scholarly journals OVOL2 is a critical regulator of ER71/ETV2 in generating FLK1+, hematopoietic, and endothelial cells from embryonic stem cells

Blood ◽  
2014 ◽  
Vol 124 (19) ◽  
pp. 2948-2952 ◽  
Author(s):  
Ju Young Kim ◽  
Ra Ham Lee ◽  
Tae Min Kim ◽  
Dong-Wook Kim ◽  
Young-Joo Jeon ◽  
...  
Keyword(s):  
Stem Cells ◽  
Endothelial Cells ◽  
Embryonic Stem Cells ◽  
Binding Protein ◽  
Embryonic Stem ◽  
Erythroid Cells ◽  
Key Points

Key Points OVOL2 is identified as a novel binding protein of ER71. Interaction between ER71 and OVOL2 cooperatively regulates the generation of FLK1+ mesoderm, and endothelial and erythroid cells.

scholarly journals Uncovering the RNA-binding protein landscape in the pluripotency network of human embryonic stem cells

Cell Reports ◽  
2021 ◽  
Vol 35 (9) ◽  
pp. 109198
Author(s):  
Shlomi Dvir ◽  
Amir Argoetti ◽  
Chen Lesnik ◽  
Mark Roytblat ◽  
Kohava Shriki ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Human Embryonic Stem Cells ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Embryonic Stem

scholarly journals Reduced Genomic Cytosine Methylation and Defective Cellular Differentiation in Embryonic Stem Cells Lacking CpG Binding Protein

2005 ◽  
Vol 25 (12) ◽  
pp. 4881-4891 ◽  
Author(s):  
Diana L. Carlone ◽  
Jeong-Heon Lee ◽  
Suzanne R. L. Young ◽  
Erika Dobrota ◽  
Jill Sergesketter Butler ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Dna Methyltransferase ◽  
Cellular Differentiation ◽  
Cytosine Methylation ◽  
Epigenetic Modification ◽  
Binding Protein ◽  
Embryonic Stem ◽  
Growth Media ◽  
Methyltransferase Activity

ABSTRACT Cytosine methylation at CpG dinucleotides is a critical epigenetic modification of mammalian genomes. CpG binding protein (CGBP) exhibits a unique DNA-binding specificity for unmethylated CpG motifs and is essential for early murine development. Embryonic stem cell lines deficient for CGBP were generated to further examine CGBP function. CGBP − / − cells are viable but show an increased rate of apoptosis and are unable to achieve in vitro differentiation following removal of leukemia inhibitory factor from the growth media. Instead, CGBP − / − embryonic stem cells remain undifferentiated as revealed by persistent expression of the pluripotent markers Oct4 and alkaline phosphatase. CGBP − / − cells exhibit a 60 to 80% decrease in global cytosine methylation, including hypo-methylation of repetitive elements, single-copy genes, and imprinted genes. Total DNA methyltransferase activity is reduced by 30 to 60% in CGBP − / − cells, and expression of the maintenance DNA methyltransferase 1 protein is similarly reduced. However, de novo DNA methyltransferase activity is normal. Nearly all aspects of the pleiotropic CGBP − / − phenotype are rescued by introduction of a CGBP expression vector. Hence, CGBP is essential for normal epigenetic modification of the genome by cytosine methylation and for cellular differentiation, consistent with the requirement for CGBP during early mammalian development.

Positive regulators of the lineage-specific transcription factor GATA-1 in differentiating erythroid cells

1994 ◽  
Vol 14 (5) ◽  
pp. 3108-3114
Author(s):  
M H Baron ◽  
S M Farrington
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Transcription Factor ◽  
Embryonic Stem Cells ◽  
Cultured Cells ◽  
Globin Gene ◽  
Embryonic Stem ◽  
Targeted Mutagenesis ◽  
Erythroid Cell ◽  
Erythroid Cells

The zinc finger transcription factor GATA-1 is a major regulator of gene expression in erythroid, megakaryocyte, and mast cell lineages. GATA-1 binds to WGATAR consensus motifs in the regulatory regions of virtually all erythroid cell-specific genes. Analyses with cultured cells and cell-free systems have provided strong evidence that GATA-1 is involved in control of globin gene expression during erythroid differentiation. Targeted mutagenesis of the GATA-1 gene in embryonic stem cells has demonstrated its requirement in normal erythroid development. Efficient rescue of the defect requires an intact GATA element in the distal promoter, suggesting autoregulatory control of GATA-1 transcription. To examine whether GATA-1 expression involves additional regulatory factors or is maintained entirely by an autoregulatory loop, we have used a transient heterokaryon system to test the ability of erythroid factors to activate the GATA-1 gene in nonerythroid nuclei. We show here that proerythroblasts and mature erythroid cells contain a diffusible activity (TAG) capable of transcriptional activation of GATA-1 and that this activity decreases during the terminal differentiation of erythroid cells. Nuclei from GATA-1- mutant embryonic stem cells can still be reprogrammed to express their globin genes in erythroid heterokaryons, indicating that de novo induction of GATA-1 is not required for globin gene activation following cell fusion.

scholarly journals Endothelial cells derived from embryonic stem cells respond to cues from topographical surface patterns

2013 ◽  
Vol 7 (1) ◽  
pp. 18 ◽  
Author(s):  
Rachel Hatano ◽  
Kevin Mercurio ◽  
Jesus Luna ◽  
Drew E Glaser ◽  
Valerie J Leppert ◽  
...  
Keyword(s):  
Stem Cells ◽  
Endothelial Cells ◽  
Embryonic Stem Cells ◽  
Embryonic Stem ◽  
Surface Patterns

scholarly journals Definitive-like erythroid cells derived from human embryonic stem cells coexpress high levels of embryonic and fetal globins with little or no adult globin

Blood ◽  
2006 ◽  
Vol 108 (5) ◽  
pp. 1515-1523 ◽  
Author(s):  
Kai-Hsin Chang ◽  
Angelique M. Nelson ◽  
Hua Cao ◽  
Linlin Wang ◽  
Betty Nakamoto ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Human Embryonic Stem Cells ◽  
Molecular Mechanisms ◽  
Embryoid Body ◽  
Fetal Liver ◽  
Embryonic Stem ◽  
Erythroid Differentiation ◽  
Erythroid Cells ◽  
Promising Tool

Human embryonic stem cells are a promising tool to study events associated with the earliest ontogenetic stages of hematopoiesis. We describe the generation of erythroid cells from hES (H1) by subsequent processing of cells present at early and late stages of embryoid body (EB) differentiation. Kinetics of hematopoietic marker emergence suggest that CD45+ hematopoiesis peaks at late D14EB differentiation stages, although low-level CD45- erythroid differentiation can be seen before that stage. By morphologic criteria, hES-derived erythroid cells were of definitive type, but these cells both at mRNA and protein levels coexpressed high levels of embryonic (ϵ) and fetal (γ) globins, with little or no adult globin (β). This globin expression pattern was not altered by the presence or absence of fetal bovine serum, vascular endothelial growth factor, Flt3-L, or coculture with OP-9 during erythroid differentiation and was not culture time dependent. The coexpression of both embryonic and fetal globins by definitive-type erythroid cells does not faithfully mimic either yolk sac embryonic or their fetal liver counterparts. Nevertheless, the high frequency of erythroid cells coexpressing embryonic and fetal globin generated from embryonic stem cells can serve as an invaluable tool to further explore molecular mechanisms.

scholarly journals Wnt signaling promotes hematoendothelial cell development from human embryonic stem cells

Blood ◽  
2008 ◽  
Vol 111 (1) ◽  
pp. 122-131 ◽  
Author(s):  
Petter S. Woll ◽  
Julie K. Morris ◽  
Matt S. Painschab ◽  
Rebecca K. Marcus ◽  
Aimee D. Kohn ◽  
...  
Keyword(s):  
Stem Cells ◽  
Endothelial Cells ◽  
Embryonic Stem Cells ◽  
Wnt Signaling ◽  
Human Embryonic Stem Cells ◽  
Stromal Cells ◽  
Hematopoietic Cells ◽  
Embryonic Stem ◽  
Canonical Wnt Signaling ◽  
Canonical Wnt

Human embryonic stem cells (hESCs) provide an important means to effectively study soluble and cell-bound mediators that regulate development of early blood and endothelial cells in a human model system. Here, several complementary methods are used to demonstrate canonical Wnt signaling is important for development of hESC-derived cells with both hematopoietic and endothelial potential. Analyses using both standard flow cy-tometry, as well the more detailed high-throughput image scanning flow cytometry, characterizes sequential development of distinct early developing CD34brightCD31+Flk1+ cells and a later population of CD34dimCD45+ cells. While the CD34brightCD31+Flk1+ have a more complex morphology and can develop into both endothelial cells and hematopoietic cells, the CD34dimCD45+ cells have a simpler morphology and give rise to only hematopoietic cells. Treatment with dickkopf1 to inhibit Wnt signaling results in a dramatic decrease in development of cells with hematoendothelial potential. In addition, activation of the canonical Wnt signaling pathway in hESCs by coculture with stromal cells that express Wnt1, but not use of noncanonical Wnt5-expressing stromal cells, results in an accelerated differentiation and higher percentage of CD34brightCD31+Flk1+ cells at earlier stages of differentiation. These studies effectively demonstrate the importance of canonical Wnt signaling to mediate development of early hematoendothelial progenitors during human development.

scholarly journals Neuroprotective Effects of Mesenchymal Stem Cells Derived from Human Embryonic Stem Cells in Transient Focal Cerebral Ischemia in Rats

2009 ◽  
Vol 29 (4) ◽  
pp. 780-791 ◽  
Author(s):  
Yi-Ping Liu ◽  
Hakan Seçkin ◽  
Yusuf İzci ◽  
Zhong Wei Du ◽  
Yi-Ping Yan ◽  
...  
Keyword(s):  
Stem Cells ◽  
Endothelial Cells ◽  
Mesenchymal Stem Cells ◽  
Embryonic Stem Cells ◽  
Cerebral Ischemia ◽  
Human Embryonic Stem Cells ◽  
Focal Cerebral Ischemia ◽  
Embryonic Stem ◽  
Transient Focal Cerebral Ischemia ◽  
Infarction Volume

Embryonic mesenchymal stem cells (eMSCs) were first derived from human embryonic stem cells (hESCs) overexpressing green fluorescence protein (GFP). They expressed CD29, CD44, CD73, CD105, CD166 and nestin, but not CD34, CD45, CD106 SSEA-4 or Oct3/4. Twenty million eMSCs in 1mL of phosphate-buffered saline (PBS) were injected into the femoral veins of spontaneously hypertensive rats after transient middle cerebral artery occlusion. The migration and differentiation of the eMSCs in the ischemic brain were analyzed. The results revealed that eMSCs migrated to the infarction region and differentiated into neurons, which were positive for β-tubulin III, microtubule-associated protein 2 (MAP2), HuC, neurofilament and human nuclear antibody, and to vascular endothelial cells, which were positive for von Willebrand factor (vWF). The transplanted cells survived in the infarction region for at least 4 weeks. Adhesive removal function significantly improved in the first week after cell transplantation, and rotarod motor function significantly improved starting from the second week. The infarction volume in the eMSC group was significantly smaller than that in the PBS control group at 4 weeks after infusion. The results of this study show that when administered intravenously, eMSCs differentiated into neuronal and endothelial cells, reduced the infarction volume, and improved behavioral functional outcome significantly in transient focal cerebral ischemia.

Primitive and Definitive Erythropoiesis

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. SCI-37-SCI-37
Author(s):  
James Palis
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Embryonic Stem ◽  
Yolk Sac ◽  
Erythroid Cells ◽  
Transient Wave ◽  
Self Renewal ◽  
Primitive Erythropoiesis ◽  
Definitive Erythropoiesis

Abstract Abstract SCI-37 Studies in mammalian and nonmammalian vertebrate embryos indicate that erythropoiesis comes in two flavors: primitive and definitive. The primitive erythroid lineage in mammalian embryos is characterized by a transient wave of lineage-committed progenitors that emerge from the yolk sac and generate a wave of precursors that synchronously mature in the bloodstream. Primitive erythroid precursors dynamically regulate embryonic globin gene expression and ultimately enucleate to form erythrocytes. Primitive erythropoiesis is superseded by definitive erythroid cells that mature extravascularly in association with macrophage cells. Studies in the mouse embryo indicate that definitive erythropoiesis has two distinct developmental origins. The first is a transient wave of erythro-myeloid progenitors (EMP) that emerge from the yolk sac and seed the early fetal liver. The second is a long-term program of erythropoiesis derived from hematopoietic stem cells. Erythropoietin is the central regulator of definitive erythropoiesis, in part by regulating the survival of committed progenitors. In contrast, the role of erythropoietin in primitive erythropoiesis remains poorly understood. Recent studies indicate that erythropoietin does not regulate the primitive erythroid progenitor compartment, but rather plays a critical role in establishing an antiapoptotic state during the terminal maturation of primitive erythroblasts. EMP-derived proerythroblasts are capable of extensive self-renewal in vitro, while primitive erythroid progenitors are incapable of self-renewal under the same conditions. These studies, taken together, indicate that the primitive and definitive forms of erythropoiesis have fundamental differences in the regulation of red cell output. The overlapping emergence of primitive and definitive erythroid lineages in differentiating embryonic stem cells suggests that the transient yolk-sac-derived primitive and EMP-derived definitive erythroid programs are recapitulated in vitro. These studies offer the hope that human embryonic stem cells can serve as a source of functional definitive erythroid cells for transfusion therapy. Disclosures: No relevant conflicts of interest to declare.

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