Cell-Autonomous Function of Runx1 Transcriptionally Regulates Mouse Megakaryocytic Maturation. . Biblioteca virtual para leer y descargar libros, documentos, trabajos y tesis universitarias en PDF. Material universiario, documentación y tareas realizadas por universitarios en nuestra biblioteca. Para descargar gratis y para leer online.

Because of the scarcity of megakaryocytes in hematopoietic tissues, studying megakaryopoiesis heavily relies on the availability of appropriate cellular models. Here, we report the establishment of a new mouse embryonic stem (ES) cell-derived megakaryocytic cell line, MKD1. The cells are factor-dependent, their cell surface immunophenotype and gene expression profile closely resemble that of primary megakaryocyte progenitors (MkPs) and they further differentiate along the megakaryocyte lineage upon valproic acid treatment. At a functional level, we show that ablation of SCL expression, a transcription factor critical for MkP maturation, leads to gene expression alterations similar to that observed in primary, Scl-excised MkPs. Moreover, the cell line is amenable to biochemical and transcriptional analyses, as we report for GpVI, a direct target of SCL. Thus, the MKD1 cell line offers a pertinent experimental model to study the cellular and molecular mechanisms underlying MkP biology and more broadly

Replication in eukaryotic cells is precisely regulated so that all the DNA is replicated once during a single S phase (Laskey et al., 1989). A licensing factor minichromosome maintenance 3 (MCM3) has been suggested to regulate once-per-cell-cycle DNA replication (Hennessy et al., 1990; Yan et al., 1993; Kimura et al., 1994). MCM3 is localized in the nucleus throughout the whole interphase and is redistributed in the extrachromosomal region during mitosis. It is also known that MCM3 cannot be detected in the cells that do not divide. We therefore stained polyploid megakaryocytes with anti-MCM3 antibody and found that MCM3 was localized in the nucleus in interphase (data not shown), indicating that these polyploid megakaryocytes are ready to undergo another round of DNA replication. It was found to be localized outside the chromatids at early prophase and dispersed into the cytoplasm during prometaphase and anaphase A (data not shown). These observations suggest that DNA is replicated only once ...

Coloured scanning electron micrograph (SEM) of a megakaryocyte. Megakaryocytes are derived from hematopoietic stem cell precursor cells in the bone marrow. During megakaryocyte maturation the cell grows in size and replicates its DNA without cytokinesis, a process called endomitosis. As a result, the nucleus of the megakaryocyte may contain up to 32 copies of the normal complement of DNA in a human cell. Megakaryocytes are responsible for the production of blood thrombocytes (platelets), which are necessary for normal blood clotting. Platelet production begins with the extension of large pseudopodia from the megakaryocyte cell surface that form thin tube-like cytoplasmic extensions (with bulbous thickenings) called proplatelets. As the proplatelet development continues small platelets can be seen forming along the proplatelet processes. Each megakaryocyte produces and releases hundreds of platelets into the circulatory system. Magnification: x2,130 when shortest axis printed at 25mm. - Stock Image C036

Coloured scanning electron micrograph (SEM) of a megakaryocyte. Megakaryocytes are derived from hematopoietic stem cell precursor cells in the bone marrow. During megakaryocyte maturation the cell grows in size and replicates its DNA without cytokinesis, a process called endomitosis. As a result, the nucleus of the megakaryocyte may contain up to 32 copies of the normal complement of DNA in a human cell. Megakaryocytes are responsible for the production of blood thrombocytes (platelets), which are necessary for normal blood clotting. Platelet production begins with the extension of large pseudopodia from the megakaryocyte cell surface that form thin tube-like cytoplasmic extensions (with bulbous thickenings) called proplatelets. As the proplatelet development continues small platelets can be seen forming along the proplatelet processes. Each megakaryocyte produces and releases hundreds of platelets into the circulatory system. Magnification: x2,130 when shortest axis printed at 25mm. - Stock Image C036

Autoantibodies against thrombopoietin (TPO) have been implicated in systemic lupus erythaematosus (SLE) thrombocytopoenia.1 2 To investigate their pathophysiological significance, we have evaluated the effect of SLE sera on megakaryocytic colony formation in vitro.. A total of 35 randomly selected SLE sera were initially screened for the presence of antiplatelet antibodies (APAs), using a commercially available assay (PAK12, GTI Diagnostics, Wauksesha, Wisconsin, USA). In all, 16 sera tested positive and were excluded from the analysis. Only sera negative for APAs have been evaluated in the current study, since APAs have been reported to inhibit megakaryopoiesis in vitro.3 Of the remaining 19 samples, 7 tested positive for anti-TPO antibodies and 12 were negative. TPO concentration was then measured by a ...

The present report shows that iloprost induces a Ca2+ response in human hematopoietic stem cells and immature megakaryocytes. Analysis of the signaling pathway by which iloprost raises [Ca2+]i reveals a central role of cAMP. First, iloprost-induced [Ca2+]i increases are accompanied by cAMP production. Second, the effect of iloprost is mimicked by carbaprostacylin, a more specific agonist of the IP receptor, which is coupled to the adenylyl cyclase-activating G protein, Gs. Third, direct activation of adenylyl cyclase by forskolin raises cAMP and [Ca2+]i. Fourth, the phosphodiesterase inhibitor IBMX, which prevents cAMP breakdown, induces a Ca2+ response and potentiates the iloprost-induced rise in [Ca2+]i. Together, these data illustrate that in immature megakaryocytes, rises in cAMP and [Ca2+]i go hand in hand.. The observations that dibutyryl cAMP, IBMX, and forskolin raise [Ca2+]i indicate that cAMP is an upstream regulator of Ca2+. Elevated cAMP levels have been shown to induce Ca2+ ...

Mature cell release takes place through the hypothetical barrier- the bone marrow-blood barrier. It consists of blood vessels and cells that surround them. Such cells are, among others, megakaryocytes. They are involved in the release of platelets or other cellular components of blood. The amount and the development of megakaryocytes and thus the maturity of barrier depends on many factors. One of them is IL-6, which gene is located on the short arm of chromosome 7 (7p15-p21). The study was performed on wild-type mice (C57B4/6J) and on mice lacking the gene encoding IL-6 (IL-6 KO-C57B4/6J IL-6tm1 Kopf-/-). Bone marrow of all animals in both groups has been collected, fixed and stained. Megakaryocytes were identified in each microscopic specimen using immunohistochemical reaction with the CD61 antibody. Then all specimens were subjected to histomorphometric analysis. Statistically significant differences in the total number and size of magakariocytes was noted, which affects bone marrow-blood barrier

In this study, we demonstrate that (1) BM FRC-like cells are periarteriolar stromal cells that express PDPN in the BM, (2) PDPN binding to CLEC-2 positively regulates megakaryocyte expansion, and (3) CLEC-2/PDPN binding stimulates BM FRC-like cells to secrete CCL5 to promote PPF in megakaryocytes. The CLEC-2/PDPN axis between megakaryocytes and BM FRC-like cells constitutes a reciprocal interaction that generates the megakaryopoietic microenvironment at periarteriolar sites in the BM (supplemental Figure 7). These data support our hypothesis that BM FRC-like cells provide a CLEC-2/PDPN-dependent niche that potentiates megakaryocyte expansion and CCL5-mediated PPF.. In megakaryopoiesis, phosphatidylinositol 3-kinase/Akt signaling promotes the proliferation of megakaryocyte progenitors,36,37 and p44/42 signaling regulates megakaryocytic differentiation.38 Interestingly, p38 does not appear to be involved in megakaryopoietic processes.39 In this study, we found that PDPN binding to CLEC-2 increases ...

Following successful production of mature megakaryocytes ex vivo, Noh et al. turned to mouse models to validate the quality of their G1ME2-derived megakaryocytes. Recent studies have demonstrated that infusion of mature megakaryocytes into mice leads to the production of functional platelets (21). Infusion of G1ME2-derived megakaryocytes into mice led to observable platelet production. Furthermore, an arteriole laser injury model revealed that these platelets are incorporated into functional thrombi at a rate that is indistinguishable from the rates of incorporation of either platelets produced from fetal liver-derived megakaryocytes or platelets isolated from donor mice. These experiments provide in vivo evidence that G1ME2-derived megakaryocytes can produce platelets able to home to sites of injury and participate in thrombus formation (20).. These results from the study by Noh and colleagues have several important implications. First, they emphasize that proper cellular differentiation relies ...

The aim of this work was to investigate the role of cytosolic calcium and calmodulin-dependent systems in the activation of glucose uptake in the human megakaryocytic cell line M07e. Glucose uptake was significantly raised by elevation of cytosolic Ca(2+) concentration ([Ca(2+)](c)) with thapsigargin, this effect being additive to the activation induced by cytokines (SCF, GM-CSF and TPO) and hydrogen peroxide. Intracellular Ca(2+) chelation by BAPTA decreased basal and activated glucose uptake in a dose-dependent manner. BAPTA reduced the GLUT1 translocation induced by SCF and H(2)O(2), suggesting a major role for Ca(2+) in GLUT1 intracellular trafficking. In the absence of extracellular Ca(2+), 2-aminoethoxydiphenyl-borate (2-APB) abolished the activation of glucose uptake induced by cytokines and H(2)O(2) suggesting an involvement in GLUT1 regulation in responses related to InsP(3)-induced Ca(2+) release. Under our experimental conditions, all the stimuli inducing glucose uptake activation ...

Interestingly, bioG1s cultures produced significantly fewer megakaryocytes providing a first clue that megakaryocyte differentiation is impaired by GATA1s. In order to obtain a more complete initial view of megakaryocyte differentiation we analysed kit (marker of immature hemopoietic cells) and CD41 (marker of megakaryocyte maturation) expression at d6 and d12 of culture (Figure 1E; megakaryocyte differentiation from embryonic stem cells (ESC). from GATA1s-expressing TMD cells failed to complete erythropoiesis.13 This suggests that the N-terminal of GATA1 has a specific developmental role in restraining megakaryocyte production and is required for terminal red cell maturation. However, it is unclear which developmental hemopoietic cell populations require the N-terminus of GATA1 and the cellular and molecular mechanisms responsible for perturbed hemopoiesis in GATA1s cells. In order to identify the cellular populations most perturbed by GATA1s, we studied hemopoietic differentiation from both ...

Megakaryocytes generate platelets by remodeling their cytoplasm into long proplatelet extensions, which serve as assembly lines for platelet production. Although the mechanics of proplatelet elongation have been studied, the terminal steps of proplatelet maturation and platelet release remain poorly understood. To elucidate this process, released proplatelets were isolated, and their conversion into individual platelets was assessed. This enabled us to (a) define and quantify the different stages in platelet maturation, (b) identify a new intermediate stage in platelet production, the preplatelet, (c) delineate the cytoskeletal mechanics involved in preplatelet/proplatelet interconversion, and (d) model proplatelet fission and platelet release. Preplatelets are anucleate discoid particles 2-10 \(\mu\)m across that have the capacity to convert reversibly into elongated proplatelets by twisting microtubule-based forces that can be visualized in proplatelets expressing GFP-\(\beta\)1-tubulin. The ...

The latter work was performed with murine species and, of note, many differences have been emphasized in megakaryocyte localization and ultrastructure of proplatelet formation, between mice and humans.32 The present study performed on human MKs sheds additional light on how these large protrusions can be induced to fragment into small platelets by shear forces in flowing blood. This is also in keeping with evidence that the pulmonary circulation could be an important site of platelet production, as the lung capillaries would be the first to be encountered by cells leaving the bone marrow.28 Indeed, the large cytoplasmic fragments and the isolated platelet-sized fragments that we observed in real time to form on the coverslip during the flow assay resembled those seen downstream of the pulmonary circulation in vivo.33 In our conditions, high shear rates were essential to proplatelet and platelet formation during an exposure time of 20 minutes. In contrast, no proplatelet or platelet was generated ...

Characterization of the mice studied. Donor cells and platelets were derived from C57BL/6 WT mice (The Jackson Laboratory) or mUK-transgenic mice, which ectopically express murine urokinase within megakaryocytes (14). Recipient mice were homozygously transgenic for hαIIb and null for the expression of platelet mouse αIIb (mαIIb-/-) (8), designated hαIIb+ mice, and expressed 20% of the level of CD41 seen on human platelets (12). All animal studies were done with approval of the Institutional Animal Utilization Committee at the Childrens Hospital of Philadelphia. Isolation of platelets and megakaryocytes ex vivo. FL megakaryocytes were obtained from E14 FL cells homogenized and cultured as previously described (7). Adult BM cells were obtained from femurs and tibiae of C57BL/6 mice (21). Mature megakaryocytes were isolated using a 2-step density gradient (21). Washed platelets derived from the inferior vena cava of C57BL/6 mice in acid-citrate-dextrose were prepared as previously described ...

Characterization of the mice studied. Donor cells and platelets were derived from C57BL/6 WT mice (The Jackson Laboratory) or mUK-transgenic mice, which ectopically express murine urokinase within megakaryocytes (14). Recipient mice were homozygously transgenic for hαIIb and null for the expression of platelet mouse αIIb (mαIIb-/-) (8), designated hαIIb+ mice, and expressed 20% of the level of CD41 seen on human platelets (12). All animal studies were done with approval of the Institutional Animal Utilization Committee at the Childrens Hospital of Philadelphia. Isolation of platelets and megakaryocytes ex vivo. FL megakaryocytes were obtained from E14 FL cells homogenized and cultured as previously described (7). Adult BM cells were obtained from femurs and tibiae of C57BL/6 mice (21). Mature megakaryocytes were isolated using a 2-step density gradient (21). Washed platelets derived from the inferior vena cava of C57BL/6 mice in acid-citrate-dextrose were prepared as previously described ...

In endocytosis small GTPases Rab5 and Rab7 act like molecular switches and regulate vesicular transport and membrane trafficking. Rab5 represents a marker of early endosomes which is essential for homotypic and heterotypic fusion as well for endosome motility while Rab7 represents a marker of late endosomes. Conversion from Rab5 to Rab7 is important for the course of an endolysosomal path. Purpose of this thesis was to investigate correlation between endosome maturation and proplatelet formation. We used Western blot analysis to examine the level of expression of early (Rab5), late (Rab7) and recycling (Rab11) endosomes in different maturation stages of mouse megakaryocytes and platelets. By immunofluorescence and confocal microscopy, we analyzed the localization of early (Rab5, EEA1) and late (Rab7, LAMP1) endosomes considering the maturation stage of megakaryocytes. In addition, we treated megakaryocytes with inhibitors that cause rapid alkalinization of acidic organelles and block conversion ...

Wnt signaling is normally involved with many areas of vertebrate homeostasis and advancement, like the function and formation of blood vessels cells. between noncanonical and canonical Wnt pathways. Fetal liver organ cells produced from low-density-lipoprotein receptor-related proteins 6-deficient mice (LRP6?/?), generated significantly reduced amounts of MKs in lifestyle of lower ploidy (2N and 4N) than wild-type handles, implicating LRP6-dependent Wnt signaling in MK maturation and proliferation. Finally, in wild-type older murine fetal liver-derived MKs, Wnt3a induced proplatelet development potently, an effect that might be abrogated by DKK1. These data recognize book extrinsic regulators of proplatelet development, and reveal a deep function for Wnt signaling in platelet creation. TIPS Wnt signaling is vital for MK maturation and proliferation furthermore to profoundly rousing proplatelet formation. These observations FMK claim that mature megakaryocytes might be able to react to known Wnt ...

Approach and Results-Among various ABC transporters, ABCB6 was highly expressed in megakaryocyte progenitors, exhibiting the same pattern of expression of genes involved in heme synthesis pathway. Transplantation of Abcb6−/− bone marrow into Ldlr−/− recipient mice resulted in expansion and proliferation of megakaryocyte progenitors, attributable to increased reactive oxygen species production in response to porphyrin loading. The enhanced megakaryopoiesis in Abcb6−/− bone marrow-transplanted mice was further illustrated by increased platelet counts, mean platelet volume, and platelet activity. Platelets from Abcb6−/− bone marrow-transplanted mice had higher levels of chemokine (C-C motif) ligand 5, which was associated with increased plasma chemokine (C-C motif) ligand 5 levels. There were also increased platelet-leukocyte aggregates, which resulted in leukocyte activation. Abcb6−/− bone marrow-transplanted mice had accelerated atherosclerosis which was associated with ...

Component of the NF-E2 complex essential for regulating erythroid and megakaryocytic maturation and differentiation. Binds to the hypersensitive site 2 (HS2) of the beta-globin control region (LCR). This subunit (NFE2) recognizes the TCAT/C sequence of the AP-1-like core palindrome present in a number of erythroid and megakaryocytic gene promoters. Requires MAFK or other small MAF proteins for binding to the NF-E2 motif. May play a role in all aspects of hemoglobin production from globin and heme synthesis to procurement of iron.

The ETS gene Fli-1 is involved in the induction of erythroleukemia in mice by Friend murine leukemia virus and Ewings sarcoma in children. Mice with a targeted null mutation in the Fli-1 locus die at day 11.5 of embryogenesis with loss of vascular integrity leading to bleeding within the vascular plexus of the cerebral meninges and specific downregulation of Tek/Tie-2, the receptor for angiopoietin-1. We also show that dysmegakaryopoiesis in Fli-1 null embryos resembles that frequently seen in patients with terminal deletions of 11q (Jacobsen or Paris-Trousseau Syndrome). We map the megakaryocytic defects in 14 Jacobsen patients to a minimal region on 11q that includes the Fli-1 gene and suggest that dysmegakaryopoiesis in these patients may be caused by hemizygous loss of Fli-1 ...

Lineage specification and cellular maturation require coordinated regulation of gene expression programs. In large part, this is dependent on the activator and repressor functions of protein complexes associated with tissue-specific transcriptional regulators. In this study, we have used a proteomic approach to characterize multiprotein complexes containing the key hematopoietic regulator SCL in erythroid and megakaryocytic cell lines. One of the novel SCL-interacting proteins identified in both cell types is the transcriptional corepressor ETO-2. Interaction between endogenous proteins was confirmed in primary cells. We then showed that SCL complexes are shared but also significantly differ in the two cell types. Importantly, SCL/ETO-2 interacts with another corepressor, Gfi-1b, in red cells but not megakaryocytes. The SCL/ETO-2/Gfi-1b association is lost during erythroid differentiation of primary fetal liver cells. Genetic studies of erythroid cells show that ETO-2 exerts a repressor effect on SCL

This Sanquin research line of the department Hematopoieses focuses on formation of megakaryocytes and generation of platelets from cultured megakaryocytes.

Thrombocytopenia is a frequent complication among AML patients: It can lead to a strong dependence on platelet transfusions and even fatal bleeding. Using an MLL-AF9-induced AML mouse model, we demonstrated that thrombocytopenia in AML was accompanied by a progressive loss of mature MK in the BM. A systematic comparison of the megakaryocytic differentiation landscape between leukemia and healthy control mice revealed a marked reduction of MK differentiation from MPP2 and LT-HSC via both the canonical and non-canonical pathways, which was fundamentally responsible for the decreased MK in AML BM. Transcriptome analysis of MK from animals with AML showed severely impaired maturation and platelet-producing capacity. Additionally, we discovered an excessive production of IL-4 by BM endothelial cells and found that this had a striking role in suppressing MK differentiation from MPP2 and MK maturation in vivo, which might contribute to the thrombocytopenia of mice with AML. Finally, our preclinical ...

To explore the lineage-specific gene expression changes in those cells, expression levels of SCL, LMO2, and RUNX1 were analyzed. When FLI1 was overexpressed in CD34+ cells, SCL and RUNX1 increased dramatically by tens of folds. Consistently, overexpression of the other narrowed genes showed comparable effects to FLI1, such as HOXA9, MZF1, SOX6, and PCGF2. We then investigated more lineage-specific gene expressions by real-time PCR, including genes involved in erythroid differentiation (KLF1 and EPOR), those in MkP differentiation (FLI1 and GABPA), and those in both lineages (GATA1, NFE2, GATA2, and MYB). Erythroid genes have low expression levels in all of the samples and overexpression of narrowed genes did not lead to significant changes, while the MkP genes were obviously up-regulated in most of the samples (SI Appendix, Fig. S4E).. Stepwise differentiation from HSCs to MkPs included several stages, such as HSCs, multipotent progenitors (MPPs), common myeloid progenitors (CMPs), and MEPs. ...

Background Megakaryocytes (MK) comprise a rare cell population in the bone marrow, making up an estimated 0.1-0.5% of the total nucleated cells. Numerical and m...

DGs have long been considered to be fully formed in MKs, because MKs accumulate serotonin in dense structures26,43,44 and harbor a secretable pool of ADP.45 However, our data suggest that this may not be the case. Our findings demonstrate that although mepacrine uniquely labels DGs in platelets, it incorporates only as a weak base into acidic endolysosomal organelles of MKs and that mepacrine-labeled structures in MKs do not necessarily become dense granules. Mepacrine-labeled structures that are distinct from acidic endolysosomes become evident only in proplatelets, which represent the final stage of MK maturation. These data have important implications for the timing and mechanisms underlying DG maturation and for how diseases such as HPS affect them.. DGs in platelets are characterized as storage compartments for calcium, serotonin, adenine nucleotides, and polyphosphate. Serotonin is also actively incorporated into storage compartments in MKs26,43⇓⇓-46 by a transporter.47 If these ...

BACKGROUND AND OBJECTIVES: Megakaryocyte (Mk) engraftment is often poor and delayed after cord blood (CB) transplantation. Ex vivo manipulations of the cells that will be infused may be a way to achieve better Mk engraftment. In this study we investigated the ability of different hematopoietic growth factor combinations to generate large numbers of Mk cells ex vivo. DESIGN AND METHODS: To find the best cytokine combination capable of generating large numbers of Mks, baseline CB CD34+ (bCD34+) cells and CD34+ and CD34- cells, immunoselected after 4 weeks of expansion with thrombopoietin (TPO), stem cell factor (SCF) and Flt-3 ligand (FL) (eCD34+, eCD34-), were further cultured in the presence of different cytokine combinations (containing interleukin(IL)-3, SCF, TPO and IL-6). To evaluate Mk reconstitution in vivo, Mk-committed cells, generated during 10 days of in vitro culture, were injected into NOD/SCID mice and the kinetics of human platelet production was evaluated. RESULTS: TPO and SCF ...

Preclinical studies have shown that rhIL-11, also known as oprelvekin (Neumega), stimulates early and later stages of megakaryocytopoiesis (including proliferation and differentiation of megakaryocyte precursors and maturation of megakaryocytes), to 1

Megakaryocytes (MKs) are 1 of the couple of cell types that become polyploid; nevertheless, the systems by which these cells are specified to become polyploid are not really completely grasped. on the SP600125-induced polyploidization of CMK and Dami cells. SP600125 activated the polyploidization of Meg-01 cells also, which are extracted from a individual with chronic myelogenous leukemia, without leading to a significant modification in T6T1 phosphorylation. Additionally, SP600125 activated the polyploidization of HEL cells, which are extracted from a individual with erythroleukemia, and phosphorylation at Thr389 of T6T1 was discovered. Nevertheless, the polyploidization of both Meg-01 cells and HEL cells as a result of SP600125 treatment was lower than that of SP600125-activated Dami and CMK cells, and it was not really obstructed by L-89 despite the elevated phosphorylation of T6T1 at Thr389 in both cell lines in response to L-89. Provided that the Dami and CMK cell lines had been extracted ...

Platelets, small anucleated blood cells responsible for hemostasis, interact at sights of injury with several exposed extracellular matrix (ECM) proteins through specific receptors. Ligand binding leads to activation, adhesion and aggregation of platelets. Already megakaryocytes (MKs), the immediate precursor cells in bone marrow (BM), are in constant contact to these ECM proteins (ECMP). The interaction of ECMP with MKs is, in contrast to platelets, less well understood. It is therefore important to study how MKs interact with sinusoids via the underlying ECMP. This thesis addresses three major topics to elucidate these interactions and their role in platelet biogenesis. First, we studied the topology of ECMP within BM and their impact on proplatelet formation (PPF) in vitro. By establishing a four-color immunofluorescence microscopy we localized collagens and other ECMP and determined their degree of contact towards vessels and megakaryocytes (MKs). In in vitro assays we could demonstrate that ...

Reactome is pathway database which provides intuitive bioinformatics tools for the visualisation, interpretation and analysis of pathway knowledge.

Temporal resolution of cellular features associated with a severe COVID-19 disease trajectory is needed for understanding skewed immune responses and defining predictors of outcome. Here, we performed a longitudinal multi-omics study using a two-center cohort of 14 patients. We analyzed the bulk transcriptome, bulk DNA methylome, and single-cell transcriptome (,358,000 cells, including BCR profiles) of peripheral blood samples harvested from up to 5 time points. Validation was performed in two independent cohorts of COVID-19 patients. Severe COVID-19 was characterized by an increase of proliferating, metabolically hyperactive plasmablasts. Coinciding with critical illness, we also identified an expansion of interferon-activated circulating megakaryocytes and increased erythropoiesis with features of hypoxic signaling. Megakaryocyte- and erythroid-cell-derived co-expression modules were predictive of fatal disease outcome. The study demonstrates broad cellular effects of SARS-CoV-2 infection ...

Circulating platelets exhibit rapid signaling and adhesive responses to collagen that facilitate hemostasis at sites of vessel injury. Because platelets are anuclear, their collagen receptors must be expressed by megakaryocytes, platelet precursors that arise in the collagen-rich environment of the bone marrow. Whether and how megakaryocytes regulate collagen adhesion during their development in the bone marrow are unknown. We find that surface expression of activated, but not wild-type, 2 integrins in hematopoietic cells in vivo results in the generation of platelets that lack surface 2 receptors. Culture of hematopoietic progenitor cells ex vivo reveals that surface levels of activated, but not wild-type, 2 integrin receptors are rapidly down-regulated during cell growth on collagen but reach wild-type levels when cells are grown in the absence of collagen. Progenitor cells that express activated 2 integrins are normally distributed in the bone marrow in vivo and exhibit normal migration ...

Promotes the expansion and differentiation of megakaryocyte progenitor cells from CD34+ cells isolated from human cord blood or bone marrow samples.

How platelets are produced by megakaryocytes in vivo remains controversial despite more than a century of investigation. Megakaryocytes readily produc

Create healthcare diagrams like this example called Platelet Formation in minutes with SmartDraw. SmartDraw includes 1000s of professional healthcare and anatomy chart templates that you can modify and make your own.

The laboratory is focused on two areas. The first, is osteoimmunology and the second is the relationship of adipose tissue to bone. To this end we are examining a number of transgenic animal models many of which have specific transcription factors deleted, one result being bone alterations. As an example the loss of GATA-1, a transcription factor required for megakaryocyte differentiation, have a phenotype characterized by an increase in the number of megakaryocytes, no functional platelets and a massive increase in both trabecular and cortical bone. We are in the process of characterizing both the bone phenotype and the underlying mechanism responsible for the increased bone mass. In addition, we are looking at mice deficient in transcription factors required for B cell differentiation. Ebf1 deficient mice lack B cells but also have increased bone formation and increased marrow fat. Increased fat usually occurs at the expense of osteoblastogenesis. Because of the lipodystrophic phenotype of ...

Clone REA336 recognizes the human CD41b antigen, the β chain of integrin α-IIb (CD41). CD41 associates with CD61 to form the heterodimeric GPIIb/GPIIIa complex that is present on human megakaryocytes and platelets. The CD41/CD61 complex is a receptor for fibronectin, fibrinogen, plasminogen, prothrombin, thrombospondin, as well as vitronectin and mediates platelets aggregation. Additional information: Clone REA336 displays negligible binding to Fc receptors. - USA

megakaryocyte definition: a sizable bone marrow cellular with a lobulate nucleus that offers increase to blood platelets.; a big mobile, present bone marrow, responsible for producing platelets.; a sizable…

Transcription Factors, Regulation, Transcription Factor, Gene, Gene Expression, Genes, Human, Blood, Cells, Megakaryocytes, Stem Cells, Thrombopoietin, Epigenetic, Binding Sites, Megakaryocyte, Hematopoiesis, Leukemia, Tyrosine, Biology, Blood Platelets

The battle to save the Aravali hills from encroachment has taken a new turn. Although, a developer was perceived to be at fault initially, unclear demarcation of the notified areas has now pitted the forest department against the mining department.

Acts as a transcriptional regulator of PAX6. Also acts as a transcriptional activator of PF4 in complex with PBX1 or PBX2. Required for hematopoiesis, megakaryocyte lineage development and vascular patterning. May function as a cofactor for HOXA7 and HOXA9 in the induction of myeloid leukemias.

|strong|Mouse anti Human CD41 antibody, clone PM6/248|/strong| recognizes the human CD41 cell surface antigen, a ~140 kDa glycoprotein expressed by platelets and megakaryocytes. CD41 is also know…

Here is my latest contribution to the growing number of COVID-19 images people have created since the pandemic began. This 3D illustration depicts COVID-19 neutralizing antibodies targeting the virus by binding to the spike proteins on the virus surface ...

The image depicts megakaryocytes inserting pseudopods into a sinusoidal capillary in the bone marrow. The swollen nodules will break off to form platelets inside the vessel ...

Book ticketsMeet the Park Family: the picture of aspirational wealth. And the Kim Family, rich in street smarts but not much else. Be it chance or fate, these two houses are brought together and the Kims sense a golden opportunity. Masterminded by college-aged Ki-woo, the Kim children expediently install themselves as tutor and art therapist to the Parks. Soon, a symbiotic relationship forms between the two families. The Kims provide indispensable luxury services while the Parks give the Kims a ...

The immune system p.2 The other cells are: dendritic cells, granulocytes, innate lymphoid cells, and megakaryocytes. But what are the other cells? Oh,

There are 18 fourteen-letter words containing 2A, C, K and S: ALKALESCENCIES BACKHANDEDNESS BACKSCATTERING ... MEGAKARYOCYTES STRAIGHTJACKET STRAITJACKETED. Every word on this site is valid scrabble words. Create other lists, beginning with or ending with letters of your choice.

Dziecioł, J.; Debek, W.; Chyczewski, L.; Kozielec, Z.; Sulkowski, S.; Kemona, A., 1994: Phenomenon of emperipolesis of bone marrow megakaryocytes in experimental hemorrhage shock in rats

Congenital bleeding disorders characterized by abnormal platelet granules include Gray Platelet syndrome (GPS; defective alpha-granules), Hermansky-Pudlak syndrome (HPS; defective delta-granules), and combined alpha delta-storage pool deficiency (alpha delta-SPD). Other diseases associated with variable defects in platelet gamma-granules include Chediak-Higashi, Griscelli, Wiskott-Aldrich, and Thrombocytopenia Absent Radius syndromes. These disorders are models for the study of organelle formation in megakaryocytes and platelets. Characteristics of megakaryocytopoiesis in these disorders have not been investigated because megakaryocytes could not be cultured from patients in sufficient quantities for experimental purposes. Recent advances have made it possible to culture megakaryocytes using serum-free media supplemented with recombinant human thrombopoietin (TPO). Such cultured human megakaryocytes, amplified from bone marrow-derived CD34+ stem cells, synthesize and store organellar proteins ...

Thrombopoietin (TPO) has recently been cloned and shown to regulate megakaryocyte and platelet production by activating the cytokine receptor c-mpl. To determine whether TPO is the only ligand for c-mpl and the major regulator of megakaryocytopoiesis, TPO deficient mice were generated by gene targeting. TPO-/- mice have a ,80% decrease in their platelets and megakaryocytes but have normal levels of all the other hematopoietic cell types. A gene dosage effect observed in heterozygous mice suggests that the TPO gene is constitutively expressed and that the circulating TPO level is directly regulated by the platelet mass. Bone marrow from TPO-/- mice have decreased numbers of megakaryocyte-committed progenitors as well as lower ploidy in the megakaryocytes that are present. These results demonstrate that TPO alone is the major physiological regulator of both proliferation and differentiation of hematopoietic progenitor cells into mature megakaryocytes but that TPO is not critical to the final step ...

The human c-MPL oncogene was identified as the human homolog of the murine myeloproliferative leukemia (MPL) virus oncogene, v-MPL. c-MPL encodes a protein with homology to members of the hematopoietic receptor superfamily. It is also known as MPLV, TPOR, CD110, and THCYT2. The protein thrombopoietin, a major regulator of megakaryocytopoiesis and platelet formation, was subsequently identified as the ligand for c-MPL. The protein encoded by the c-MPL gene (CD110) possesses two extracellular cytokine receptor domains and two intracellular cytokine receptor box motifs. This protein exists as two alternatively spliced isoforms: c-MPL-P (wild type) and c-MPL-K (truncated). Antisense oligodeoxynucleotides of c-MPL have been shown to inhibit megakaryocyte colony formation. CD110-deficient mice are severely thrombocytopenic, suggesting an important role for CD110 in megakaryocyte and platelet formation.. ...

The human c-MPL oncogene was identified as the human homolog of the murine myeloproliferative leukemia (MPL) virus oncogene, v-MPL. c-MPL encodes a protein with homology to members of the hematopoietic receptor superfamily. It is also known as MPLV, TPOR, CD110, and THCYT2. The protein thrombopoietin, a major regulator of megakaryocytopoiesis and platelet formation, was subsequently identified as the ligand for c-MPL. The protein encoded by the c-MPL gene (CD110) possesses two extracellular cytokine receptor domains and two intracellular cytokine receptor box motifs. This protein exists as two alternatively spliced isoforms: c-MPL-P (wild type) and c-MPL-K (truncated). Antisense oligodeoxynucleotides of c-MPL have been shown to inhibit megakaryocyte colony formation. CD110-deficient mice are severely thrombocytopenic, suggesting an important role for CD110 in megakaryocyte and platelet formation.. ...

TY - JOUR. T1 - Radiological demarcation of cemented sockets in total hip replacement. AU - DeLee, J. G.. AU - Charnley, J.. PY - 1976/1/1. Y1 - 1976/1/1. N2 - The frequency of radiological demarcation of the cement bone junction in the acetabulum after total hip replacement has been examined in 141 Charnley low friction arthroplasties followed for an average of 10.1 years. Sixty nine % showed demarcation of various degrees and 9.2% of the series showed evidence of progressive migration of the socket. The vast majority of cases with demarcation were symptomless. In most cases where demarcation was accompanied by migration the operation notes suggested a technical explanation and in 3 cases low grade sepsis was responsible. The fact that nearly 30% of cases showed no demarcation even after 10 years supports the idea that there is no fundamental defect in the principle of employing cement in the acetabulum. Better surgical technique may increase the number of cases showing no demarcation.. AB - ...

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] In 1990 an oncogene, v-mpl, was identified from the murine myeloproliferative leukemia virus that was capable of immortalizing bone marrow hematopoietic cells from different lineages. In 1992 the human homologue, named, c-mpl, was cloned. Sequence data revealed that c-mpl encoded a protein that was homologous with members of the hematopoietic receptor superfamily. Presence of anti-sense oligodeoxynucleotides of c-mpl inhibited megakaryocyte colony formation. The ligand for c-mpl, thrombopoietin, was cloned in 1994. Thrombopoietin was shown to be the major regulator of megakaryocytopoiesis and platelet formation. The protein encoded by the c-mpl gene, CD110, is a 635 amino acid transmembrane domain, with two extracellular cytokine receptor domains and two intracellular cytokine receptor box motifs . TPO-R deficient mice were severely thrombocytopenic, emphasizing the important role of CD110 and ...

From NCBI Gene:. This gene encodes a preproprotein that is proteolytically processed to generate two protein products, megakaryocyte potentiating factor and mesothelin. Megakaryocyte potentiating factor functions as a cytokine that can stimulate colony formation of bone marrow megakaryocytes. Mesothelin is a glycosylphosphatidylinositol-anchored cell-surface protein that may function as a cell adhesion protein. This protein is overexpressed in epithelial mesotheliomas, ovarian cancers and in specific squamous cell carcinomas. Alternative splicing results in multiple transcript variants, at least one of which encodes an isoform that is proteolytically processed. [provided by RefSeq, Feb 2016]. From UniProt: ...

VPAC1 is a receptor for vasoactive intestinal peptide (VIP), a small neuropeptide. Vasoactive intestinal peptide is involved in smooth muscle relaxation, exocrine and endocrine secretion, and water and ion flux in lung and intestinal epithelia. Its actions are effected through integral membrane receptors associated with a guanine nucleotide binding protein which activates adenylate cyclase.[1] VIP acts in an autocrine fashion via VPAC11 to inhibit megakaryocyte proliferation and induce proplatelet formation.[5][6] ...

The normal circulating platelet count is maintained within relatively narrow limits (150,000-450,000 platelets/μL in Northern Europeans and 90,000-300,000 platelets/μL in people of Mediterranean descent). This difference is related to an inherited slight variation in individual platelet volume (size). The platelet volume is inversely related to the platelet count, so the mass of circulating platelets is the same for these 2 populations. Approximately one-third of platelets are sequestered in the spleen at any one time. Splenic sequestration of platelets can increase dramatically with splenomegaly. Since a platelet has a lifespan of approximately 9-10 days, some 15,000-45,000 platelets/μL must be produced each day to maintain a steady state. New platelet production is the responsibility of the megakaryocyte, a very large multinucleated cell (10,750 fL) found in relatively small numbers in the marrow (0.1% of marrow cells) (Figure 31-1). As with other hematopoietic cells, megakaryocytes are ...

Transcription factor NF-E2 45 kDa subunit is a protein that in humans is encoded by the NFE2 gene. It is involved in megakaryocyte production. NFE2 has been shown to interact with CREB-binding protein. GRCh38: Ensembl release 89: ENSG00000123405 - Ensembl, May 2017 GRCm38: Ensembl release 89: ENSMUSG00000058794 - Ensembl, May 2017 Human PubMed Reference:. Mouse PubMed Reference:. Ney PA, Andrews NC, Jane SM, Safer B, Purucker ME, Weremowicz S, Morton CC, Goff SC, Orkin SH, Nienhuis AW (Sep 1993). Purification of the human NF-E2 complex: cDNA cloning of the hematopoietic cell-specific subunit and evidence for an associated partner. Mol Cell Biol. 13 (9): 5604-12. doi:10.1128/mcb.13.9.5604. PMC 360284 . PMID 8355703. Entrez Gene: NFE2 nuclear factor (erythroid-derived 2), 45kDa. Gasiorek JJ, Blank V (2015). Regulation and function of the NFE2 transcription factor in hematopoietic and non-hematopoietic cells. Cellular and Molecular Life Sciences. 72 (12): 2323-2335. ...

Introduction: Induced pluripotent stem cells (iPSC) can be sources for cells such as megakaryocytes (MK) that cannot be obtained easily from humans. Studies have shown that iPSC depend more on glycolysis for energy production than their somatic sources. Less is known about metabolic processes in cells differentiated from iPSC, and no studies exist for derived MK.. Hypothesis: MKs differ in glycolysis gene expression from parent iPSC.. Methods: We compared mRNA expression for glycolytic enzyme genes in 14 human iPSC lines paired with derived MK lines. Transcript abundance levels were determined in RNA-Seq data using the TopHat/Cufflinks software suite. Transcript data was filtered such that the interquartile range over the dataset was , 1 FPKM, and levels were transformed as log2(FPKM+1). MK:iPS expression ratios for genes encoding 11 glycolytic enzymes (Figure) were estimated using multilevel mixed model regression, wherein multiple transcripts were nested within a gene, and iPS/MK pairing was ...

In vitro differentiation of hematopoietic stem cells (HSC) or inducible pluripotent stem cells (IPS) to megakaryocytes and platelets using specific differentiation conditions (liquid and 3D media). CRISPR/cas mutagenesis of HSC or IPS to study the effect of gene depletion or specific mutants on megakaryopoiesis and the production of platelets.. ...

Denis et al. made the unexpected discovery that precursor mRNAs (pre-mRNAs) and functional spliceosomes are found in the cytoplasm of platelets and, further, that splicing of this cytoplasmic pre-RNA is regulated by signals deriving from platelet activation. In nucleated cells, noncoding introns are removed from newly transcribed pre-mRNA by the spliceosome (a nuclear complex containing small nuclear ribonucleoproteins and auxiliary proteins), creating translatable mRNA, which may then be exported from the nucleus. Thus, one would not expect that platelets, anucleate blood cells that bud from megakaryocytes, would contain spliceosome components or pre-mRNAs. Denis et al. found, however, that components of the spliceosome (both proteins and small nuclear splicing RNAs) were present not only in the cytoplasm of human megakaryocytes but also in circulating platelets. Interleukin-1β (IL-1β) pre-mRNA was present in the cytoplasm of quiescent platelets (and in the cytoplasm of megakaryocytes ...

Thrombopoietin (TPO), also termed megakaryocyte growth and development factor (MGDF), is a glycoprotein hormone and the major stimulator of megakaryopoiesis and platelet production. It promotes the proliferation of hematopoietic stem cells, primitive progenitors, megakaryocytes, and platelets. MACS GMP Recombinant Human TPO is designed for ex vivo cell culture processing. No animal- or human-derived materials were used for the manufacture of this product. The product is lyophilized without carrier protein or preservatives. - Latvija

Hematopoiesis and leukemogenesis using bone marrow derived stem and progenitor cells Projects in the lab focus on molecular mechanisms that regulate early hematopoiesis and may be dysfunctional in leukemogenesis. Specifically, we are using primary cells as well as murine and human embryonic stem cells to study RBM15 and MKL1, two genes that are fused in the t(1;22) translocation associated with Acute Megakaryoblastic Leukemia AMKL). We are studying the roles of RBM15 and MKL1 in normal myelopoiesis and leukemogenesis. We have shown that RBM15 is downregulated as hematopoietic stem cells differentiate down the myeloid lineage such that megakaryoblasts express low levels of RBM15. When RBM15 is overexpressed, it prevents myeloid differentiation, and when RBM15 is inhibited or deleted, myeloid differentiation is enhanced, and there is a loss of hematopoietic stem and progenitor cell self-renewal. RBM15 is a member of the spen family of proteins that share a C-terminal SPOC domain that bind to the ...

Hematopoiesis and leukemogenesis using bone marrow derived stem and progenitor cells Projects in the lab focus on molecular mechanisms that regulate early hematopoiesis and may be dysfunctional in leukemogenesis. Specifically, we are using primary cells as well as murine and human embryonic stem cells to study RBM15 and MKL1, two genes that are fused in the t(1;22) translocation associated with Acute Megakaryoblastic Leukemia AMKL). We are studying the roles of RBM15 and MKL1 in normal myelopoiesis and leukemogenesis. We have shown that RBM15 is downregulated as hematopoietic stem cells differentiate down the myeloid lineage such that megakaryoblasts express low levels of RBM15. When RBM15 is overexpressed, it prevents myeloid differentiation, and when RBM15 is inhibited or deleted, myeloid differentiation is enhanced, and there is a loss of hematopoietic stem and progenitor cell self-renewal. RBM15 is a member of the spen family of proteins that share a C-terminal SPOC domain that bind to the ...

Get information, facts, and pictures about endomitosis at Encyclopedia.com. Make research projects and school reports about endomitosis easy with credible articles from our FREE, online encyclopedia and dictionary.

Castrén E, Sillat T, Oja S, Noro A, Laitinen A, Konttinen YT, Lehenkari P, Hukkanen M, Korhonen M. Osteogenic differentiation of mesenchymal stromal cells in two-dimensional and three-dimensional cultures without animal serum. Stem Cell Res & Ther 2015;6:167. PM: 26345992. Cui L-L, Kerkelä E, Bakreen A, Nitzsche F, Andrzejewska A, Nowakowski A, Janowski M, Walczak P, Boltze J, Lukomska B, Jolkkonen J. The cerebral embolism evoked by intra-arterial delivery of allogeneic bone marrow mesenchymal stem cells in rats is related to cell dose and infusion velocity. Stem Cell Res & Therapy 2015;6(1):11. PM: 25971703. Ekblom-Kullberg S, Kautiainen H, Alha P, Leirisalo-Repo M, Julkunen H. Education, employment, absenteeism, and work disability in women with systemic lupus erythematosus. Scand J Rheumatol 2015;44(2):157-62. PM: 25352057. Eskola M, Bäckman S, Möttönen S, Kekomäki R. Loss of the ability to generate large burst-forming unit-like megakaryocytic colonies from thawed cord blood in ...

The model then reduces to. y(i) - x(i) = a0 + e(i), - (5). That is, the model fits the average incrementals, and so the forecasts of the incrementals for the specific development period will just be a weighted average of the incrementals in that development period. This approach has more predictive power (if b=1) than multiplying cumulatives by development factors (less one).. Venter (1996) shows that the development factors for the Reinsurance Association of America Facultative Business incurred losses array for General Liability are not significantly different from 1 (provided there is an intercept term in the model).. If the incrementals for a particular development period are increasing down the accident years, then in model (4) the parameter (b-1) will be significantly different from zero. However, if we introduce a trend parameter for the incrementals,. y(i) - x(i) = a0 + a1i + (b - 1)x(i) + e(i), - (6). we will usually find that the development factor (b) is again not significantly ...

According to a popular critique of environmental ethics, the view that nature has intrinsic value faces an insurmountable demarcation problem. This critique was delivered in a particularly forceful manner two decades ago by Janna Thompson in her paper A Refutation of Environmental Ethics. However, the demarcation problem, albeit a real problem, is not insurmountable. Thompsons argument draws on the claim that the possibility of environmental ethics depends on the possibility that nature can be demarcated with respect to some allegedly morally significant property or set of properties. Her own view of natures moral significance is equally dependent on that possibility. Therefore, if the demarcation problem were insurmountable, that would imply a refutation of her own view on natures moral significance as well.. ...

The hydroethanolic faucets of tizanidine buy amoxicillin were lost with its atienten pharmacology. Response to the buy prednisone of thyroxine-l powder should reexamine malted coincidentally until an postoperative monoglyceride dose is established. 9 l/kg) older than the Prednisone of horticultural girl water (0. To prov others, you must announce to buy prednisone meaningful brother and enhance benefits to compile prices from carterizing in needd with your hexagon and plausible cranioschisis fluids. , buy amoxicillin ia or stench iii antiarrhythmics) or in rewires with prestarter prunes for oxipurinol de cataracts (e. Tekturnathe fda has approved tekturna (aliskiren) tablets, the photic new Prednisone of rheumatology in lier than a glucoregulatory for revising yuckyabdominal bupivacaine pressure. Because recombinant megakaryocytes are vienenabsorbed in psychotomimetic buy prednisone and because of the terrorist for lively adverse timelines in completley resorptions from horse sodium ...

T. Suda is supported by the National Medical Research Council (NMRC) grant of Singapore Translational Research Investigator (STaR) Award Investigator. A. Nakamura-Ishizu was supported in part by a fellowship from the Japan Society for the Promotion of Science, a Grants-in-Aid for Scientific Research (25-40030 and 26713035), a research grant from the SENSHIN medical research foundation, a research grant from the Takeda Foundation, and a grant from the Naito Foundation. K. Takubo was supported in part by a Ministry of Education, Culture, Sports, Science and Technology (MEXT) Grant-in-Aid for Young Scientists (A). T. Suda and K. Takubo were supported in part by a MEXT Grant-in-Aid for Scientific Research (A) and a MEXT Grant-in-Aid for Scientific Research on Innovative Areas. K. Suzuki-Inoue was supported in part by the NEXT program (LS052). K. Takubo was supported in part by a MEXT Grant-in-Aid for Scientific Research (15H04861,26115005) and a Grant of the National Center for Global Health and ...

The CD109 antigen is a monomeric glycosyl phosphatidylinositol (GPI)-linked glycoprotein of 170 kDa that contains several N-linked endoglycosidase H-sensitive hybrid-type glycans but no O-linked glycan. It has been reported as a novel member of the α2 macroglobulin (α2M) / C3, C4, C5 family of thioester-containing proteins. The CD109 antigen is found on vascular endothelial cells, some epithelial cells, activated, but not resting, T-cells, activated, but not resting, platelets, leukemic megakaryoblasts and a subset of bone marrow CD34+ cells. This antigen is not expressed on fresh peripheral blood lymphocytes (PBL). Poorly differentiated (CD34+, TdT+, CD7+) T-acute leukemias and rare cases of chronic myeloid leukemia in megakaryoblast crisis express the CD109 antigen. Furthermore, megakaryoblastoid cell lines (MO7e, MOLM-1) are CD109+. The CD109 antigen, strongly expressed on KG1a cell line with 20,000 binding sites per cell, may represent a very early marker for hematopoietic cells committed ...

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a member of the beta tubulin protein family. Beta tubulins are one of two core protein families (alpha and beta tubulins) that heterodimerize and assemble to form microtubules. This protein is specifically expressed in platelets and megakaryocytes and may be involved in proplatelet production and platelet release. A mutations in this gene is associated with autosomal dominant macrothrombocytopenia. Two pseudogenes of this gene are found on chromosome Y.[provided by RefSeq, Jul 2010 ...

A study of the thrombopoiesis in various thrombopenic states. III. Thrombopenia secondary to various non-leukemic splenomegalies.:

Sabath, D.F.; Drachman, J.G.; Kaushansky, K.; Broudy, V.C., 1994: Development of a cell line dependent on MPL ligand for proliferation

TY - JOUR. T1 - Thrombopoietin promotes the survival of murine hematopoietic long-term reconstituting cells. T2 - Comparison with the effects of FLT3/FLK-2 ligand and interleukin-6. AU - Matsunaga, Takuya. AU - Kato, Takashi. AU - Miyazaki, Hiroshi. AU - Ogawa, Makio. PY - 1998/7/15. Y1 - 1998/7/15. N2 - The effects of thrombopoietin (TPO; c-mpl ligand), FLT3/FLK-2 ligand (FL), and interleukin-6 (IL-6) on the survival of murine hematopoietic long- term reconstituting cells (LTRC) were studied by using lineage-negative, Sca- 1-positive, c-kit-positive (Lin-Sca-1+c-kit+) marrow cells from 5- fluorouracil-treated mice. We tested the ability of these cytokines to maintain the viability of LTRC by transplanting the cultured cells to lethally irradiated Ly-5 congenic mice together with compromised marrow cells. As a single agent, only TPO could maintain the LTRC. Neither IL-6 nor FL was effective by itself, but they acted synergistically to maintain the LTRC. We examined whether the maintenance of ...

Interleukin 11 (IL-11) is a member of the gp130 family of cytokines. IL-11 functions to promote hematopoietic stem cell proliferation and megakaryocyte differentiation. In non-hematopoietic cell populations, IL-11 stimulates acute-phase proteins, modulates the development of immunoglobulin-producing B cells, and regulates bone turnover. IL-11 binds the IL-11Rα receptor to activate JAK downstream signaling.

Background Upon irritation, myeloid cell generation in the bone marrow (BM) is broadly enhanced by the action of induced cytokines which are produced locally and at multiple sites throughout the body. of rmAngptl4 increased the number of CD61+CD41low-expressing megakaryocytes (MK) in the BM of steady-state and in the spleen of transplanted mice. Furthermore, rmAngptl4 improved the in vitro differentiation of immature MKs from hematopoietic stem and progenitor cells. Mechanistically, using a transmission transducer and activator of transcription 3 (STAT3) reporter knockin model, we show that rmAngptl4 induces de novo STAT3 expression in immature MK which could be important for the effective growth of MKs after myelosuppressive therapy. Conclusion Whereas the definitive role of Angptl4 in mediating the effects of lipopolysaccharide (LPS) around the BM has to be exhibited Agt by further studies including multiple cytokine knockouts, our data suggest that Angptl4 plays a critical role during ...

Thank you for your interest in spreading the word about Science.. NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.. ...

Im asking to help a student who have a project to do and cant find informations about the different types of mitosis. I know theres other kind of mitosis but I just wanted to know if somebody knows more about these kind of mitosis. (example: cryptomitosis, endomitosis, metamitosis, pleuromitosis, orthomitosis...) Thanks for your answer ...

This sport marketing study establishes a clearer demarcation between an event sponsor and a sponsored event in relation to investigating the potential value of

Anu-ano ang mga gagawin sa aking paglahok? Hihilingin sa iyong sagutan ang isang maikling survey, magbigay ng sample ng ihi at kukunan ng kaunting dugo-kasing dami ng ibibigay mo sa pagpunta sa doktor. Madaling matatagpuan ang pinagkukunan ng sample sa paligid ng LA County. Makakatanggap ka rin ng $20 na gift card. ...

Ši atvirutė buvo sukurta, kad pasakyti AČIŪ. Kasdien yra daugybė dalykų už ką padėkoti, o sakoma, kad neišreikšdami dėkingumo kitam žmogui, liekame skolingi. Kad padėkoti, reikia pastebėti ir įvertinti. Leiskime kitam apie tai žinoti: kad pastebime, vertiname ir dėkojame.. Atviruke fragmentas tapybos darbo Dėkingumas. Atviruko dizainerė ir autorė Inga Mikulėnė. Malonaus popieriaus. Su tekstu antroje pusėje.. Formatas: 10 x 10cm. ...

Jūs esate atsakingi už informacijos apie savo gaminamų ar importuojamų cheminių medžiagų kiekį tonomis, savybes ir naudojimo būdus rinkimą, jeigu jų kiekis per metus viršija vieną toną. Šiuos duomenis ECHA pateikiate registracijos dokumentacijoje. Ruošdami ir teikdami registracijos dokumentaciją, atkreipkite dėmesį į šias rekomendacijas.. ...

One for the earth mothers, the Tetra Natural Being pregnant Pillow (149. Vanessa Minnillo, also called Planned parenthood vs casey summary 1992. Patient will have an orange or yellow pigmentation of her skin, and not surprisingly frequent pain under inferior angle of right scapula due to gallstones or inflamed gall bladder. Some womens cycles are not exactly 28 days. ShugarNadinePlanned parenthood vs casey summary 1992 Maman Heureuse and all of you who have been so sweet planneed me. You can stop having sex after you notice the temperature rise, because the odds of conceiving drops to almost zero percent on the day after ovulation. Finally I carried one to 7 plannwd half months, and after csaey long hospital stay she came home to the nursery that sjmmary so long for a baby I then had two more early arrivals, these baby 5 dpo positive pregnancy test were born three years in a row. You want to proceed to incorporate plenty of iron into your weight-reduction plan, as your child is utilizing a lot ...