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  • stem cell
  • Paralleling efforts to guide pluripotent stem cell differentiation by manipulating developmental cues, substantial progress has been made recently toward HSC generation via combinatorial transcription factor (TF)‐mediated fate conversion, a paradigm established by Yamanaka's induction of pluripotency in somatic cells by mere four TFs. (embopress.org)
  • Within the hematopoietic stem cell (Lin − Sca-1 + c-Kit + ) compartment these lineage-specific transcription factors are expressed at low levels but are up-regulated with the process of lineage specification. (bloodjournal.org)
  • The invention provides means of manipulating hematopoietic stem cell differentiation by modulation of levels of NR2F6 (EAR2). (freepatentsonline.com)
  • Soluble hJagged-1 inhibited myeloid colony formation but not erythroid-mix or erythroid colony formation, in the presence of stem cell factor (SCF), interleukin-3, granulocyte-macrophage colony-stimulating factor (GM-CSF), G-CSF, thrombopoietin, and erythropoietin. (springer.com)
  • Moreover, interleukin-17A (IL-17A) promotes both granulocyte-colony stimulating factor (G-CSF)- and stem-cell-factor-mediated neutrophilia ( 6 ) and supports G-CSF-driven "emergency" myelopoiesis ( 7 ). (frontiersin.org)
  • 2004). Gfi1 plays a major role in the stem cell fraction, B-, T- and myeloid compartment, whereas it is relatively low expressed in the megakaryocytic-erythroid compartment. (atlasgeneticsoncology.org)
  • 7 Institute for Stem Cell and Regenerative Medicine Research, Albert Einstein College of Medicine, Bronx, NY 10461, USA. (sciencemag.org)
  • The authors also determined the mechanism linking iron chelation to hematopoietic stem cell maintenance, which may help facilitate the development of future treatments. (sciencemag.org)
  • Finally, we suggest that disruption of stem cell regulatory programs is likely to play an important role in many other pathologies including ageing-associated regenerative failure. (springer.com)
  • Primary colonies could be replated for at least three generations in vitro and established primitive myelomonocytic cell lines upon transfer into suspension cultures supplemented with interleukin‐3 and stem cell factor. (embopress.org)
  • Though several components of the stem cell niche have been identified, the regulatory mechanisms through which such components regulate the stem cell fate are still unknown. (jove.com)
  • Chronic myelogenous leukemia (CML) is a clonal myeloproliferative disorder of the pluripotent hematopoietic stem cell clinically characterized by the accumulation of myeloid precursors in peripheral blood, bone marrow, and extramedullary sites. (aacrjournals.org)
  • We found that by providing a humanized environment, stem cell self-renewal properties were better maintained as determined by serial transplantation assays and genome-wide transcriptome studies, and less clonal drift was observed as determined by exome sequencing. (bloodjournal.org)
  • endothelial cells
  • In order to study the contribution of Tie1 to tumor progression and metastasis, we conditionally deleted Tie1 in endothelial cells at different stages of tumor growth and metastatic dissemination. (jci.org)
  • 1 - 5 Similarly, after cutaneous injury, a heterogeneous population of BMDCs are recruited to the site of injury and contribute directly to the repair process by differentiating into skin cell types, such as fibroblasts, keratinocytes, and endothelial cells. (bloodjournal.org)
  • HOXA7 and HOXB3 are up-regulated during the differentiation of human BMD mesenchymal stem cells into endothelial cells, while HOXA3 and HOXB13 are down-regulated during differentiation. (bloodjournal.org)
  • Subsequent surges in MCT stimulated retinal endothelial cells to produce monocyte chemotactic protein-1 (MCP1) and angiogenic factors, leading to sprouting angiogenesis. (jci.org)
  • Angiogenesis is a multistep process that requires coordinated migration, proliferation, and junction formation of vascular endothelial cells (ECs) to form new vessel branches in response to growth stimuli. (jci.org)
  • CLEC14A formed a complex with VEGFR-3 in endothelial cells (ECs), and CLEC14A KO resulted in a marked reduction in VEGFR-3 that was concomitant with increases in VEGFR-2 expression and downstream signaling. (jci.org)
  • The impact of TME-dependent heterogeneity of tumor endothelial cells (TECs) on tumorigenesis is unclear. (jci.org)
  • The initial work, published in the JCI in 2000, described the method enabling successful attainment of blood outgrowth endothelial cells (BOEC). (jci.org)
  • Although VEGFR-1 and VEGFR-2 are expressed in vascular endothelial cells, monocytes, macrophages, and hematopoietic stem cells, the expression of VEGFR-3 is largely restricted to lymphatic endothelial cells consistent with a role of this receptor in lymphangiogenesis ( 4 ). (aacrjournals.org)
  • pathways
  • At the cellular level, AhR establishes functional interactions with signaling pathways governing cell proliferation and cell cycle, cell morphology, cell adhesion and cell migration. (frontiersin.org)
  • Our data suggest that oncogenic transcription factors such as HOXA9 provide a fertile ground for specific signaling pathways to thrive, explaining why JAK/STAT pathway mutations accumulate in HOXA9-expressing cells. (aacrjournals.org)
  • tumor
  • Tie1 deletion during primary tumor growth in mice led to a decrease in microvessel density and an increase in mural cell coverage with improved vessel perfusion. (jci.org)
  • Concomitantly, surgical removal of the primary tumor decreased the number of circulating tumor cells, reduced metastasis, and prolonged overall survival. (jci.org)
  • Additionally, Tie1 deletion in experimental murine metastasis models prevented extravasation of tumor cells into the lungs and reduced metastatic foci. (jci.org)
  • BMD Gr-1 + CD11b + cells function as immune suppressor cells and contribute significantly to tumor-induced neovascularization. (bloodjournal.org)
  • Our results suggest that modulation of KDR/ID2 signaling may restrict tumor-associated myeloid cells and could potentially be a therapeutic strategy for preventing transformation of premalignant gliomas. (jci.org)
  • Different tumor microenvironments (TMEs) induce stromal cell plasticity that affects tumorigenesis. (jci.org)
  • While differentiation and reprogramming of myeloid cells toward an immunosuppressive phenotype can be considered the result of a multistep process that originates in the bone marrow and culminates in the tumor microenvironment, the identification of its driving events may offer potential therapeutic approaches in different pathologies. (frontiersin.org)
  • Indeed, whereas expansion of MDSCs, in both murine and human tumor bearers, results in reduced immune surveillance and antitumor cytotoxicity, placing an obstacle to the effectiveness of anticancer therapies, adoptive transfer of MDSCs has shown therapeutic benefits in autoimmune disorders. (frontiersin.org)
  • In fact, it is possible that AhR could help modulate the balance between differentiation and pluripotency in normal and transformed tumor cells. (frontiersin.org)
  • Tumor-associated myeloid cells maintain immunosuppressive microenvironments within tumors. (jci.org)
  • Identification of myeloid-specific receptors to modulate tumor-associated macrophage and myeloid-derived suppressor cell (MDSC) functions remains challenging. (jci.org)
  • We investigated how LILRB targeting could modulate tumor-associated myeloid cell function. (jci.org)
  • Laboratory studies typically utilize tumor cell lines expressing transfected genes, or with silenced genes. (usc.edu)
  • Indeed, loss of function of many tumor suppressors regulating cell proliferation, survival, and differentiation results from aberrant mRNA processing, nuclear export, and/or translation. (aacrjournals.org)
  • CD11b+Gr1+ cells, which include neutrophils, macrophages, and myeloid-derived suppressor cells, have been shown to contribute to tumor angiogenesis. (aacrjournals.org)
  • SU11248 inhibits VEGFRs, PDGFR, c-kit, and Flt-3 and has efficacy in imatinib-resistant gastrointestinal stromal tumor ( 8 ) and renal cell carcinoma. (aacrjournals.org)
  • In addition to tumor cells, stromal cells are thought to be a source of various proangiogenic factors. (aacrjournals.org)
  • Tumor-associated fibroblasts (TAF) are an important source of stromal-derived factor 1, leading to the recruitment of endothelial progenitor cells or myeloid cells into the tumor microenvironment ( 10 ). (aacrjournals.org)
  • Also, various tumor-infiltrating hematopoietic cells such as T- and B- lymphocytes, and monocytes/macrophages have been suggested to secrete proangiogenic factors including VEGF-A ( 11 ). (aacrjournals.org)
  • proteins
  • CCAAT/enhancer-binding proteins (C/EBPs) are a family of transcription factors that regulate cell growth and differentiation in numerous cell types. (bloodjournal.org)
  • Conditional deletion of Emc3 in murine embryonic lung epithelial cells disrupted the synthesis and packaging of surfactant lipids and proteins, impaired the formation of lamellar bodies, and induced the unfolded protein response in alveolar type 2 (AT2) cells. (jci.org)
  • Transcriptomic, lipidomic, and proteomic analyses demonstrated that EMC3 coordinates the assembly of lipids and proteins in AT2 cells that is necessary for surfactant synthesis and function at birth. (jci.org)
  • Both human and murine Gfi1 proteins consist of 422 amino acids and have a mass of 45297 Da. (atlasgeneticsoncology.org)
  • mechanisms
  • Here, we describe relevant mechanisms of myeloid cell reprogramming leading to generation of suppressive MDSCs and discuss their therapeutic ductility in disease. (frontiersin.org)
  • Following epithelial cell destruction, nephrons have a limited ability to regenerate, though the mechanisms and limitations that guide this phenomenon remain poorly understood. (jove.com)
  • The high cure rate of APL is due in part to the extreme sensitivity of leukemic promyelocytes to the differentiating effects of the vitamin A derivative all - trans retinoic acid (ATRA), and it thus becomes critical to delineate the mechanisms by which APL cells respond to this and other retinoids. (springer.com)
  • Our focus here will thus be on the structure and function of the four fusion genes involved in APL pathogenesis, and on the mechanisms by which APL cells are sensitive to, and in some cases become resistant to, retinoids. (springer.com)
  • By contrast, the molecular mechanisms responsible for transition to CML-BC remain poorly understood, although a reasonable assumption is that the unrestrained activity of BCR/ABL in hematopoietic stem/progenitor cells is the primary determinant of disease progression. (aacrjournals.org)
  • Projects are ongoing on the functional effects of BM transplantation and to determine the cells and mechanisms responsible for this engraftment. (yale.edu)
  • human
  • The 5E10 monoclonal antibody reacts with human CD90, also known as Thy-1 (thymus cell antigen-1). (novusbio.com)
  • Using human atherosclerotic samples, cultured cells, and a mouse model of advanced atherosclerosis, we investigated the role of intraplaque hemorrhage on macrophage function with respect to angiogenesis, vascular permeability, inflammation, and plaque progression. (jci.org)
  • So far, few studies have focused on expression of microRNAs during HL-60 differentiation, and the expression profiles of human miRNAs during cell differentiation remain largely unknown. (beds.ac.uk)
  • Preterm infants with early retinopathy of prematurity had markedly higher plasma MCT levels than age-matched infants without disease, suggesting mast cells contribute to human disease. (jci.org)
  • In the mid-1990s, my research group began to devise a method to establish endothelial cell cultures from human peripheral blood, with an ultimate goal of examining interindividual heterogeneity of endothelial biology. (jci.org)
  • Until now, neutralizing capacity of GM-CSF autoantibodies has been assessed by evaluating the growth inhibition of human bone marrow cells or TF-1 cells stimulated with GM-CSF 6-8 . (jove.com)
  • GM-CSF binding to sGMRα was dose-dependently inhibited by polyclonal GM-CSF autoantibody in a similar manner to the bioassay using TF-1 cells, indicating that our new cell-free assay system using sGMRα is more useful for the measurement of neutralizing activity of GM-CSF autoantibodies than the bioassay system using TF-1 cell or human bone marrow cells. (jove.com)
  • The murine Polycythemia (Pcm) mutation causes a myeloproliferative disease that closely resembles human Polycythemia rubra vera. (psu.edu)
  • The cure of up to 75% of patients with APL [ 1 , 2 ] represents a remarkable and fascinating success story in medicine, and the treatment of APL with retinoic acid serves as a paradigm for the use of differentiation therapy in other types of human cancers. (springer.com)
  • 1980. Induction of differentiation of the human promyelocytic leukemia cell line (HL-60) by retinoic acid. (springer.com)
  • For this purpose, human CD34+ cells were cultured in direct contact with primary human OBs. (jove.com)
  • By implanting ceramic scaffolds coated with human mesenchymal stromal cells into immune-deficient mice, we were able to mimic the human bone marrow niche. (bloodjournal.org)
  • When the Human Erythroleukemia (HEL) cell line is induced to differentiate with TPA, overexpression of MKL1 results in an increased number of megakaryocytes with a concurrent increase in ploidy. (yale.edu)
  • Consistent with these findings in human cells, knock out of MKL1 in mice leads to reduced platelet counts, and reduced ploidy in bone marrow megakaryocytes. (yale.edu)
  • Neutrophils are the main immune cell population in adult human blood and the primary mediators of inflammatory response against invading microorganisms and foreign materials [ 14 ]. (ijbs.com)
  • assay
  • Lokeshwar, Lin: A sandwich enzyme-linked immunoadsorbent assay for detection of murine macrophage colony-stimulating factor (CSF-1). (antikoerper-online.de)
  • OBJECTIVE: To mimic GM-CSF binding to GM-CSF receptor on the cell surface using cell-free receptor-binding-assay. (jove.com)
  • RESULTS: The cell-free assay system using sGMRα yielded the data with high plasticity and reliability. (jove.com)
  • CONCLUSIONS: We established a cell-free assay quantifying the neutralizing capacity of GM-CSF autoantibody. (jove.com)
  • proliferative
  • Furthermore, the growth characteristics of cell clones allowed us to more closely and, to a certain degree, semiprospectively define cells with the highest proliferative capacity. (rupress.org)
  • regulator
  • We also identified inhibitor of DNA binding protein 2 (ID2) as a key upstream regulator of KDR activation during myeloid differentiation. (jci.org)
  • The PU.1 transcription factor is a key regulator of hematopoietic development, but its role at each hematopoietic stage remains unclear. (bloodjournal.org)
  • Traditionally considered as a critical intermediate in the toxic and carcinogenic response to dioxin (2,3,7,8-tetrachlorodibenzo- p -dioxin, TCDD), the Aryl hydrocarbon/Dioxin receptor (AhR) has proven to be also an important regulator of cell physiology and organ homeostasis. (frontiersin.org)
  • The transcription factor CCAAT/enhancer binding protein alpha (C/EBPα) is a master regulator of myeloid differentiation, and the identification of C/EBPα target genes is key to understand this process. (eur.nl)