PRINCETON, N.J. & CAMBRIDGE, Mass.--(BUSINESS WIRE)--Bristol Myers Squibb (NYSE: BMY) and Acceleron Pharma Inc. (NASDAQ: XLRN) today announced the U.S.

NFE2L2 (nuclear factor, erythroid 2-like 2), Authors: Stavroula D Manolakou, Panos G Ziros, Gerasimos P Sykiotis. Published in: Atlas Genet Cytogenet Oncol Haematol.

ADNP - ADNP (untagged)-Human activity-dependent neuroprotector homeobox (ADNP), transcript variant 1 available for purchase from OriGene - Your Gene Company.

TY - JOUR. T1 - Secretory factors from OP9 stromal cells delay differentiation and increase the expansion potential of adult erythroid cells in vitro. AU - Trakarnsanga, Kongtana. AU - Wilson, Marieangela C.. AU - Heesom, Kate J.. AU - Andrienko, Tatyana N.. AU - Srisawat, Chatchawan. AU - Frayne, Jan. PY - 2018/1/31. Y1 - 2018/1/31. N2 - Development of in vitro culture systems for the generation of red blood cells is a goal of scientists globally with the aim of producing clinical grade products for transfusion. Although mature reticulocytes can be efficiently generated by such systems, the numbers produced fall short of that required for therapeutics, due to limited proliferative capacity of the erythroblasts. To overcome this hurdle, approaches are required to increase the expansion potential of such culture systems. The OP9 mouse stromal cell line is known to promote haematopoietic differentiation of pluripotent stem cells, however an effect of OP9 cells on erythropoiesis has not been ...

TY - JOUR. T1 - Erythroid Kruppel-like factor (EKLF) coordinates erythroid cell proliferation and hemoglobinization in cell lines dervied from EKLF null mice. AU - Coghill, Elise K. AU - Eccleston, Sarah E. AU - Fox, Vanessa. AU - Cerruti, Loretta. AU - Brown, Clark. AU - Cunningham, J M. AU - Jane, Stephen. AU - Perkins, Andrew C. PY - 2001. Y1 - 2001. M3 - Article. VL - 97. SP - 1861. EP - 1868. JO - Blood. JF - Blood. SN - 0006-4971. IS - 6. ER - ...

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

We have cloned a gene, ZFF29 (zinc-finger protein of human fetal liver erythroid cells 29), from human fetal liver erythroid cells. Two types of mature mRNA were identified and designated ZFF29a and ZFF29b. In human genome the ZFF29 gene is on chromosome 9q, and the two forms are splice variants. There is a unique transcription start site, which predicts major mRNAs composed of 2485 bases for ZFF29a and 1801 bases for ZFF29b. The anticipated mRNAs were demonstrated in K562 cells, but not in any adult human tissues examined by Northern blotting. In the mouse, reverse transcription-PCR revealed that the ZFF29 mRNA is present in adult bone marrow and ovary at a higher level than in any other tissues examined. These findings suggest that ZFF29 proteins are expressed in embryonic/fetal erythroid tissues. The deduced polypeptide chains of ZFF29a and ZFF29b are composed of 306 and 350 amino acids respectively. A unique zinc-finger motif composed of two contiguous Cys2His2-type fingers is common to both ...

This communication presents a morphological study of the changes in ribosome content and organization which occur during the maturation of erythroid cells of th

A novel endoproteolytic processing activity in mitochondria of erythroid cells and the role in heme synthesis | Dzikaite, Vijole; Kanopka, Arvydas; Brock, Jeremy H.; Kazlauskas, Arunas; Melefors, OÌ jar | download | BookSC. Download books for free. Find books

On the other hand, E‐boxes are absent from an unexpectedly high proportion of TAL1 peaks (14% in Jurkat and 24% in erythroid cells) (Figure 6C). Consistent with this, the de novo motif search did not identify E‐boxes as the top overrepresented motif in erythroid or Jurkat cells (Figure 6A, left and middle panels). Instead, in erythroid cells, a Gata motif ranks first within overrepresented sites, and two variants of this motif are also among the top 7 overrepresented motifs (Figure 6A, middle panel). Furthermore, virtually all TAL1 peaks (96%) contain a Gata motif while only 76% contain an E‐box within a 100‐bp radius of the peak summit (Figure 6C). In erythroid cells, Gata motifs are also on average closer to TAL1 peak summits than E‐boxes, with 80% of TAL1 peaks containing a Gata site within 35 bp of the peak summit versus only 50% containing an E‐box within this distance (Figure 6C). This is consistent with previous studies showing cooccupation of TAL1 and GATA1 at many genomic ...

A major focus of the laboratory involves studies of erythropoiesis in real-time as stem cells undergo erythroid commitment and differentiation. It is hypothesiz...

The main finding of this work is that free uptake of the morpholino oligonucleotide ON-654 into the human erythroid cells resulted in nearly 80% of correction, a yield higher than that in syringe-loaded cells. Thus, this oligonucleotide was able to penetrate the erythroid precursor cell membrane barrier and translocate to the nucleus, suggesting that similar result should be possible in vivo. In contrast, our attempts of nuclear delivery of free negatively charged oligonucleotides were unsuccessful.. In cultured patient cells, the time course of repair by free uptake of ON-654 oligonucleotide seems to be very slow. In days 1 to 8, the repair is minimal, increasing in days 8 to 15 and even more so in days 15 to 17 (Fig. 5B). The simplest interpretation of these results is slow uptake of the morpholino oligonucleotide. However, the comparison of free uptake and syringe loading and, in particular, the analysis of intracellular localization of fluorescein-labeled oligonucleotide indicate that ...

Semantic Scholar extracted view of Cell-specific transcription and cell differentiation in the erythroid lineage. by Stuart H Orkin

Erythroid enucleation is critical for terminal differentiation of red blood cells, and involves extrusion of the nucleus by orthochromatic erythroblasts to produce reticulocytes. Due to the difficulty of synchronizing erythroblasts, the molecular mechanisms underlying the enucleation process remain poorly understood. To elucidate the cellular program governing enucleation, we utilized a novel chemical screening approach whereby orthochromatic cells primed for enucleation were enriched ex vivo and subjected to a functional drug screen using a 324 compound library consisting of structurally diverse, medicinally active and cell permeable drugs. Using this approach, we have confirmed the role of HDACs, proteasomal regulators and MAPK in erythroid enucleation and introduce a new role for Cyclin-dependent kinases, in particular CDK9, in this process. Importantly, we demonstrate that when coupled with imaging analysis, this approach provides a powerful means to identify and characterize rate limiting ...

TY - JOUR. T1 - Cell cycle exit during terminal erythroid differentiation is associated with accumulation of p27(Kip1) and inactivation of cdk2 kinase. AU - Hsieh, F. F.. AU - Barnett, L. A.. AU - Green, W. F.. AU - Freedman, K.. AU - Matushansky, I.. AU - Skoultchi, A. I.. AU - Kelley, L. L.. PY - 2000/10/15. Y1 - 2000/10/15. N2 - Progression through the mammalian cell cycle is regulated by cyclins, cyclin- dependent kinases (CDKs), and cyclin-dependent kinase inhibitors (CKIs). The function of these proteins in the irreversible growth arrest associated with terminally differentiated cells is largely unknown. The function of Cip/Kip proteins p21(Cip1) and p27(Kip1) during erythropoietin-induced terminal differentiation of primary erythroblasts isolated from the spleens of mice infected with the anemia-inducing strain of Friend virus was investigated. Both p21(cip1) and p27(Kip1) proteins were induced during erythroid differentiation, but only p27(Kip1) associated with the principal G1 CDKs - ...

Herein, we demonstrated that TET2 expression increases during erytroid differentiation of primary hematopoietic progenitors from healthy donors and MDS patients. Pronier et al. [8] demonstrated that the TET2 silencing increased granulomonocytic differentiation in detriment of erythroid differentiation in normal CD34+ cells. Yan et al. [9], similarly demonstrated that TET2 inhibition led to MDS-like dyserythropoiesis. Of note, TET2 deletion leads to erythroid dysplasia and anemia in zebrafish model [14], suggesting a conserved function for TET2 in erythrocytes production.. Recently, Guo and colleagues [15] reported that TET2 mRNA levels was increased in mature erythroid cells from murine fetal liver, and in MEL and K562 cell lines upon chemically-induced erythroid differentiation. Using functional assays, the authors also established that TET2 plays a cytoprotective function in iron homeostasis against oxidative stress during erythropoiesis. In contrast, Inokura and colleagues [16], using cell ...

The p38 MAPK subfamily is generally activated in response to environmental stresses. In most studies activation of p38 MAPKs, especially p38α isoform ultimately leads to an inflammation or an apoptotic response (30, 31). However, recent studies have shown that activation of p38α also can lead to other biological outcomes such as proliferation, cell survival, and differentiation, depending on the context and the cell type (32-39). Several studies have demonstrated that Epo induces a mitogenic response in hematopoietic cell lines through p38 MAPK pathway (23-25). However, such studies were performed using cell lines that do not recapitulate the normal growth and differentiation program. We investigated the expression, activation, and function of four isoforms of p38 MAPK by using primary erythroid progenitors that terminally differentiate into reticulocytes during in vitro culture. Interestingly, our data show that only p38α and p38γ isoforms are continuously expressed throughout ...

In this study we report the activation of c-Jun N-terminal kinase (JNK) in human K562 erythroleukemia cells undergoing hemin-mediated erythroid differentiation, which occurs concomitantly with activation of heat shock factor 2 (HSF2) and leads to a simultaneous in vivo phosphorylation of c-Jun. The activation of JNK occurs through activation of mitogen-activated protein kinase kinase (MKK) 4 and not by activation of MKK7 or inhibition of JNK-directed phosphatases. We have previously shown that overexpression of the HSF2-beta isoform inhibits the activation of HSF2 upon hemin-induced erythroid differentiation. Here we demonstrate that HSF2-beta overexpression blocks the hemin-induced activation of the MKK4-JNK pathway, suggesting an erythroid lineage-specific JNK activation likely to be regulated by HSF2. ...

The differentiation of hematopoietic progenitors into erythroid or myeloid cell lineages is thought to depend upon relative levels of the transcription factors gata1 and pu.1. While loss-of-function analysis shows that gata1 is necessary for terminal erythroid differentiation, no study has demonstrated that loss of gata1 alters myeloid differentiation during ontogeny. Here we provide in vivo evidence that loss of Gata1, but not Gata2, transforms primitive blood precursors into myeloid cells, resulting in a massive expansion of granulocytic neutrophils and macrophages at the expense of red blood cells. In addition to this fate change, expression of many erythroid genes was found to be differentially dependent on Gata1 alone, on both Gata1 and Gata2, or independent of both Gata factors, suggesting that multiple pathways regulate erythroid gene expression. Our studies establish a transcriptional hierarchy of Gata factor dependence during hematopoiesis and demonstrate that gata1 plays an integral ...

Wiens, A W.; Clintock, P R.; and Papaconstantinou, J, The dependence of erythroid differentiation on cell replication in dimethyl sulfoxide-treated friend leukemia- -virus-infected cells. (1976). Subject Strain Bibliography 1976. 2169 ...

Four proteins namely U2AF35, SRp40, mDomino and Ddx1 were identified as PHF5a interacting partners by using the murine 11.5-days embryo yeast two-hybrid library screening.PHF5a interacting domains of SR proteins U2AF35 and SRp40 were restricted to Cterminal arginine-serine rich domains (RS).Other members of the SR protein family namely SRp20, SRp30c and ASF/SF2 were shown that they can not bind to the PHF5a protein by using a directed yeast twohybrid assay and the a-galactosidase assay.Protein interactions between PHF5a and U2AF35, SRp40, mDomino and Ddx1 were verified by using in vitro coimmmunoprecipitation assays.Mapping of binding sites by using coimmunoprecipitation experiments and a directed yeast two-hybrid assay demonstrated that both ATP-dependent helicases mDomino and Ddx1 interact with the C-terminal segment of PHF5a. In addition, the N-terminal part of PHF5a was identified as a region responsible for binding to splicing proteins U2AF35 and SRp40. By using the yeast-three hybrid assay ...

The NIDDK Erythropoiesis and Hemoglobin program supports work on the molecular and cellular biological pathways involved in erythroid cell differentiation

Figure 4 Cytological analysis of electroporated OrgD3 YS-explants. Abbreviations: AFP: α-foeto-protein; Control non-electroporated YS-explants (A), maintained in organ culture, organise into a bubble-like structure that contains a compacted part, at the site adhering to the culture dish (asterisk). Erythroid cells (arrow), differentiated from explanted YS mesoderm, are located close to this adhering site (A). The bubble-like part harbours clusters similar to YS-blood islands (B: Enlargement of the square in A), which also contains erythroid cells (arrow). CD31+ cells are present in the both in the bubble-like structure and adhering site (asterisk) (C). Whereas in the adhering site, the nature of labelled cells (arrows) is unclear, CD31+ endothelial cells (D) are clearly present cells in the bubble. In electroporated YS explants, both without (E, F) or with (G, H) plasmid, the endoderm, revealed by AFP wholemount in situ hybridization, remains external, but does not cover the whole ...

a.k.a. RBCs, a.k.a. haematids, a.k.a. erythrocyte, a.k.a. erythroid cells, a.k.a. red blood corpuscles) An average Red Blood Cell measures 7.5 µm (micrometers) in diameter. An average human has 20 - 30 trillion red blood cells in their body and each cell completes a circulatory lap in about 20 seconds. ...

a.k.a. RBCs, a.k.a. haematids, a.k.a. erythrocyte, a.k.a. erythroid cells, a.k.a. red blood corpuscles) An average Red Blood Cell measures 7.5 µm (micrometers) in diameter. An average human has 20 - 30 trillion red blood cells in their body and each cell completes a circulatory lap in about 20 seconds. ...

Krueppel-like factor 1 (362, ~38 kDa) is encoded by the human KLF1 gene. This protein is involved in transcriptional regulation during erythroid cell development.

Expression of ADNP (ADNP1, KIAA0784) in cancer tissue. The cancer tissue page shows antibody staining of the protein in 20 different cancers.

ReproTeSR™, a specialized medium for iPS cell generation supports efficient reprogramming of erythroid or CD34+ cells expanded from peripheral blood.

Acute erythroid leukemia or Di Guglielmo syndrome is a rare form of acute myeloid leukemia (less than 5% of AML cases) where the myeloproliferation is of erythroblastic precursors. It is defined as type M6 under the FAB classification. The most common symptoms of AEL are related to pancytopenia (a shortage of all types of blood cells), including fatigue, infections, and mucocutaneous bleeding. Almost half of people with AEL exhibit weight loss, fever and night sweats at the time of diagnosis. Almost all people with AEL are anemic, and 77% have a hemoglobin level under 10.0 g/dl. Signs of thrombocytopenia are found in about half of people with AEL. The causes of AEL are unknown. Prior to a 2008 reclassification by the World Health Organization, cases that evolved from myelodysplastic syndromes, myeloproliferative neoplasms, chemotherapy for other cancers or exposure to toxins were defined as secondary AEL. These cases are now likely to instead be classified as acute myeloid leukemia with ...

My 11 week old son has just been diagnosed with acute erythroid leukemia, he has just received a liver transplant last week (due to inability to perform biopsy pre transplant), he will receive chemo when he recovers from transplant. Seems pretty rare, anyone know of any successful cases around as most seem to be unfortunately post mortem?. Reply Follow This Thread Stop Following This Thread Flag this Discussion ...

Objective To explore the role of Nrf2/EZH2 in mediating erythroid differentiation in mouse erythroleukemia cells under DMSO exposure. Methods MEL cells were treated with DMSO. Erythroid differentiation was detected by bezidine staining. The expression levels of Nrf2 and EZH2 were determined by western blotting. Results DMSO induced erythroid differentiation in MEL cells,along with significant induction of Nrf2 and EZH2 expression. TBHQ,a selective Nrf2 activator,increased the protein level of Nrf2.Interestingly,TBHQ also induced EZH2 expression. The lentiviral particle containing Nrf2 short hairpin RNA( shRNA) efficiently blocked TBHQ-induced EZH2 levels. Moreover,Nrf2 or EZH2 shRNA significantly inhibited DMSO-induced erythroid differentiation. Conclusion Nrf2 induction is involved in MELerythroid differentiation under DMSO exposure by regulating EZH2.

The transport and intracellular trafficking of heme biosynthesis intermediates are crucial for hemoglobin production, which is a critical process in developing red cells. Here, we profiled gene expression in terminally differentiating murine fetal liver-derived erythroid cells to identify regulators of heme metabolism. We determined that TMEM14C, an inner mitochondrial membrane protein that is enriched in vertebrate hematopoietic tissues, is essential for erythropoiesis and heme synthesis in vivo and in cultured erythroid cells. In mice, TMEM14C deficiency resulted in porphyrin accumulation in the fetal liver, erythroid maturation arrest, and embryonic lethality due to profound anemia. Protoporphyrin IX synthesis in TMEM14C-deficient erythroid cells was blocked, leading to an accumulation of porphyrin precursors. The heme synthesis defect in TMEM14C-deficient cells was ameliorated with a protoporphyrin IX analog, indicating that TMEM14C primarily functions in the terminal steps of the heme ...

Terminal erythroid differentiation is tightly coordinated with cell cycle exit, which is regulated by cyclins, cyclin-dependent kinases and cyclin-dependent kinase inhibitors (CDKI), yet their roles in erythropoiesis remain to be fully defined. We show here that p19INK4d, a member of CDKI family, is abundantly expressed in erythroblasts and that p19INK4d knockdown delayed erythroid differentiation, inhibited cell growth, led to increased apoptosis and generation of abnormally nucleated late stage erythroblasts. Unexpectedly, p19INK4d knockdown did not affect cell cycle. Rather it led to decreased expression of GATA1 protein. Importantly, the differentiation and nuclear defects were rescued by ectopic expression of GATA1. As GATA1 protein is protected by nuclear HSP70, we examined the effects of p19INK4d knockdown on HSP70 and found that p19INK4d knockdown led to decreased expression of HSP70 and its nuclear localization. The reduced levels of HSP70 are the result of reduced ERK activation. ...

Generation of red blood cells in vitro from stem cell sources.. Dr Jan Frayne.. School of Biochemistry, University of Bristol.. The generation of human red blood cells (RBCs) in vitro for transfusion purposes is a major goal of health services globally to help meet therapeutic needs. In recent years advances in the development of systems for the generation of erythrocytes in vitro have progressed rapidly using progenitor cells isolated from adult peripheral blood, umbilical cord blood and human pluripotent stem cells. Such cells can be induced to differentiate efficiently down the erythroid pathway, however detailed characterization and comprehensive analysis of the protein expression profile of such in vitro erythroid cells is required to determine how similar these cells actually are to normal erythroid cells. Furthermore, erythroid cells generated from pluripotent stem cells have differentiation and enucleation defects, the molecular basis for which are not understood. To investigate ...

Acute erythroid leukemia (AEL) is a high-risk leukemia of poorly understood genetic basis, with controversy regarding diagnosis in the spectrum of myelodysplasia and myeloid leukemia. We compared genomic features of 159 childhood and adult AEL cases with non-AEL myeloid disorders and defined five age-related subgroups with distinct transcriptional profiles: adult, TP53 mutated; NPM1 mutated; KMT2A mutated/rearranged; adult, DDX41 mutated; and pediatric, NUP98 rearranged. Genomic features influenced outcome, with NPM1 mutations and HOXB9 overexpression being associated with a favorable prognosis and TP53, FLT3 or RB1 alterations associated with poor survival. Targetable signaling mutations were present in 45% of cases and included recurrent mutations of ALK and NTRK1, the latter of which drives erythroid leukemogenesis sensitive to TRK inhibition. This genomic landscape of AEL provides the framework for accurate diagnosis and risk stratification of this disease, and the rationale for testing targeted

Embryo-fetal erythroid megaloblasts in the human coelomic cavity[1] The coelomic cavity is part of the extraembryonic mesoderm, surrounding amniotic cavity, embryo, and yolk sac in the early gestation. It is now believed to represent an important transfer interface and a reservoir of nutrients for the embryo. Coelocentesis by ultrasound-guided transvaginal puncture offers an easier access to the early human embryo, from 28 days post-fertilization. However, despite some studies about its biochemical composition being reported, our knowledge about the presence of cellular elements and their quality in this compartment are still limited. Here we studied human coelomic fluids sampled from 6.6 (48 days) to 10 weeks of gestation, demonstrating the presence of functional embryonic erythroid precursors, that is, megaloblasts in the coelomic cavity ...

Embryo-fetal erythroid megaloblasts in the human coelomic cavity[1] The coelomic cavity is part of the extraembryonic mesoderm, surrounding amniotic cavity, embryo, and yolk sac in the early gestation. It is now believed to represent an important transfer interface and a reservoir of nutrients for the embryo. Coelocentesis by ultrasound-guided transvaginal puncture offers an easier access to the early human embryo, from 28 days post-fertilization. However, despite some studies about its biochemical composition being reported, our knowledge about the presence of cellular elements and their quality in this compartment are still limited. Here we studied human coelomic fluids sampled from 6.6 (48 days) to 10 weeks of gestation, demonstrating the presence of functional embryonic erythroid precursors, that is, megaloblasts in the coelomic cavity ...

CD235a (Glycophorin A) MicroBeads can be used for the positive selection or depletion of human erythroid cells, e.g., from peripheral blood, buffy coat or cord blood. | Belgique

Erythropoietin, Erythropoiesis, Antibodies, Cell, Cells, Erythroid Progenitor Cells, Human, Progenitor Cells, Erythrocytes, Erythroid Cells, Flow Cytometry, Gene, Immunoblotting, Metabolism, Methods, Monoclonal Antibodies, Proteins, Role, Specificity, Understanding

|p|The LEGENDplex™ Mouse HSC Erythroid Panel (7-plex) is a bead-based multiplex assay panel, using fluorescence-encoded beads suitable for use on various flow cytometers. It allows for simultaneous quantification of 7 key targets involved in hematopoietic stem cell differentiation and lineage specif

Changes in the structure of gyri in the cerebral cortex are associated with various diseases and disorders. Pachygyria, lissencephaly, and polymicrogyria are all the results of abnormal cell migration associated with a disorganized cellular architecture, failure to form six layers of cortical neurons (a four-layer cortex is common), and functional problems.[6] The abnormal formation is commonly associated with epilepsy and mental dysfunctions.[7]. Pachygyria (meaning thick or fat gyri) is a congenital malformation of the cerebral hemisphere, resulting in unusually thick gyri in the cerebral cortex.[8] Pachygyria is used to describe brain characteristics in association with several neuronal migration disorders; most commonly relating to lissencephaly. Lissencephaly (smooth brain) is a rare congenital brain malformation caused by defective neuronal migration during the 12th to 24th weeks of fetal gestation resulting in a lack of development of gyri and sulci.[9]. Polymicrogyria (meaning many ...

Diamond-Blackfan anemia (DBA) is a congenital bone marrow failure syndrome characterized by erythroid hypoplasia, usually without perturbation of other hematopoietic lineages. Approximately 65% of DBA patients with autosomal dominant inheritance have heterozygous mutations or deletions in ribosomal protein (RP) genes while ,1% of patients with X-linked inheritance have been identified with mutations in the transcription factor GATA1. Erythroid cells from patients with DBA have not been well characterized, and the mechanisms underlying the erythroid specific effects of either RP or GATA1 associated DBA remain unclear. We have developed an ex vivo culture system to expand peripheral blood CD34+ progenitor cells from patients with DBA and differentiate them into erythroid cells. Cells from patients with RP or GATA1 mutations showed decreased proliferation and delayed erythroid differentiation in comparison with controls. RNA transcript analyses of erythroid cells from controls and patients with RP ...

Several pieces of evidence presented here document that β1Δ/Δ or Dko mice have an uncompensated anemia at homeostasis with signs of ineffective erythropoiesis and shortened RBC survival likely because of their inability to counteract chronic ROS accumulation. As a result, membrane changes through protein oxidation and lipid peroxidation would affect membrane fluidity and stability,3,4 leading to hemolysis. Since a similar picture is not seen in the absence of only α4-integrins ([α4β1;α4β7]−/−) the data would suggest that the absence of other integrin heterodimers in β1Δ/Δ or Dkos alone or in combination are responsible for this phenotype.. Integrins expressed in differentiated erythroid cells (mainly α4β1 and α5β1) and their interactions with fibronectin (Fn) in their ME have been previously emphasized as critical for completing terminal maturation steps.30,40,41 Specifically, on the basis of in vitro studies using fetal liver cells, it was concluded that Epo and Fn regulate ...

E-Cadherin is calcium-dependent cell adhesion molecule encoded by CDH1 gene at chromosome 16q22.1. Ecadherin regulates cell-cell adhesions and controls mobility and proli..

Isolation of fetal erythroid cells from maternal blood based on expression of erythropoietin receptors. Mol Hum Reprod, 3, 451-5.

Dr. Ans research is focused on developing a detailed molecular understanding of regulation of erythropoiesis. Her lab has developed methods to purify both human and mouse erythroid cells at distinct developmental stages and methods to quantify the progress of erythroid differentiation in vivo. Through RNA-seq analysis, her lab constructed global transcriptomesof human and murine erythroid cells. Based on the development of these novel methodology and database, Dr. Ans lab is currently working on three areas: 1) studying regulation of erythropoiesis by epigenetic modifiers such as methylcytosine dioxygenase TET2 and TET3; 2) Identifying the contribution of commonly mutated epigenetic modifiers to the dyserythropoiesis of myelodysplastic syndromes patients; 3) Improving red cell production ex vivo from stem cells.. ...

Increased fetal hemoglobin (HbF) in b-globin gene disorders ameliorates the clinical symptoms of the underlying disease. 5-azacytidine, butyrate and hydroxyurea, have been shown to activate g-globin gene expression. It has also been found that hematopoietic growth factors can influence expression of g-globin in erythroid cultures and in animal models. This study was designed to evaluate the in vitro effects of the stem cell factor (SCF) and transforming growth factor-b (TGF-b) on g-globin gene reactivation of erythroid precursors derived from CD133+ cells in vitro. Reverse Transcription-Polymerase Chain Reaction (RT-PCR) analysis showed increased expression of the g-globin transcript in cell culture groups containing either TGF- b or SCF or both as compared to control (2.2-, 2.7- and 5.5-fold, respectively) (p|0.01). Production of HbF in a differentiated population was demonstrated using flow cytometry. The results of this study suggest that SCF and TGF-b warrant further evaluation as potential

A rare point mutation in the core promoter -270GC-rich box of PIGM, a housekeeping gene, disrupts binding of the generic transcription factor (TF) Sp1 and causes inherited glycosylphosphatidylinositol (GPI) deficiency (IGD). We show that whereas PIGM messenger RNA levels and surface GPI expression in IGD B cells are low, GPI expression is near normal in IGD erythroid cells. This divergent phenotype results from differential promoter chromatin accessibility and binding of Sp1. Specifically, whereas PIGM transcription in B cells is dependent on Sp1 binding to the -270GC-rich box and is associated with lower promoter accessibility, in erythroid cells, Sp1 activates PIGM transcription by binding upstream of (but not to) the -270GC-rich box. These findings explain intact PIGM transcription in IGD erythroid cells and the lack of clinically significant intravascular hemolysis in patients with IGD. Furthermore, they provide novel insights into tissue-specific transcriptional control of a housekeeping gene by a

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 ...

Erasmus MC. Transcription Factors and Genomic Architecture. Recommended Readings. Empirical Articles. Ghamari, A., van de Corput, M. P., Thongjuea, S., van Cappellen, W. A., van IJcken, W., van Haren, J., … & Grosveld, F. G. (2013). In vivo live imaging of RNA polymerase II transcription factories in primary cells. Genes & Development, 27(7), 767-777. doi:10.1101/gad.216200.113. Mylona, A., Andrieu-Soler, C., Thongjuea, S., Martella, A., Soler, E., Jorna, R., … & Grosveld, F. (2013). Genome-wide analysis shows that Ldb1 controls essential hematopoietic genes/pathways in mouse early development and reveals novel players in hematopoiesis. Blood, 121(15), 2902-2913. doi:10.1182/blood-2012-11-467654. Nuez, B., Michalovich, D., Bygrave, A., Ploemacher, R., & Grosveld, F. (1995). Defective haematopoiesis in fetal liver resulting from inactivation of the EKLF gene. Nature, 375(6529), 316-318.. Soler, E., Andrieu-Soler, C., de Boer, E., Bryne, J. C., Thongjuea, S., Stadhouders, R., … & Grosveld, ...

The Erythron Database is a resource dedicated to facilitating better understanding of the cellular and molecular underpinnings of mammalian erythropoiesis. The resource is built upon a searchable database of gene expression in murine primitive and definitive erythroid cells at progressive stages of maturation ...

The Erythron Database is a resource dedicated to facilitating better understanding of the cellular and molecular underpinnings of mammalian erythropoiesis. The resource is built upon a searchable database of gene expression in murine primitive and definitive erythroid cells at progressive stages of maturation. ...

SMC3 G662C does not lie within any known functional domains of the Smc3 protein (UniProt.org). G662C results in significant decrease in erythroid differentiation as determined by surface expression of glycophorin A and RNA expression of fetal hemoglobin and KLF-1 in cultured cell lines (PMID: 26607380), but has not been fully biochemically characterized and therefore, its effect on Smc3 protein function is unknown ...

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Lopez-Yrigoyen M, Yang C-T, Fidanza A, Cassetta L, A Taylor H, McCahill A, Sellink E, Von Lindern M, van den Akker E, Mountford JC et al.. 2019. Genetic programming of macrophages generates an in vitro model for the human erythroid island niche.Nat Commun. 10(1):881. ...