Recombinant HoxB4 Fusion Proteins Enhance Hematopoietic Differentiation of Human Embryonic Stem Cells

2007 ◽  
Vol 16 (4) ◽  
pp. 547-560 ◽  
Author(s):  
Shi-Jiang Lu ◽  
Qiang Feng ◽  
Yordanka Ivanova ◽  
Chenmei Luo ◽  
Tong Li ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Human Embryonic Stem Cells ◽  
Fusion Proteins ◽  
Embryonic Stem ◽  
Hematopoietic Differentiation

Cells Extract from Fetal Liver Promotes the Hematopoietic Differentiation of Human Embryonic Stem Cells

2009 ◽  
Vol 11 (1) ◽  
pp. 51-60 ◽  
Author(s):  
Yu-Xiao Liu ◽  
Lei Ji ◽  
Wen Yue ◽  
Zhi-Feng Yan ◽  
Jing Wang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Human Embryonic Stem Cells ◽  
Fetal Liver ◽  
Embryonic Stem ◽  
Hematopoietic Differentiation

scholarly journals RUNX1a enhances hematopoietic lineage commitment from human embryonic stem cells and inducible pluripotent stem cells

Blood ◽  
2013 ◽  
Vol 121 (15) ◽  
pp. 2882-2890 ◽  
Author(s):  
Dan Ran ◽  
Wei-Jong Shia ◽  
Miao-Chia Lo ◽  
Jun-Bao Fan ◽  
David A. Knorr ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Human Embryonic Stem Cells ◽  
Pluripotent Stem Cells ◽  
Ex Vivo ◽  
Ectopic Expression ◽  
Embryonic Stem ◽  
Embryoid Bodies ◽  
Lineage Commitment ◽  
Hematopoietic Differentiation

Abstract Advancements in human pluripotent stem cell (hPSC) research have potential to revolutionize therapeutic transplantation. It has been demonstrated that transcription factors may play key roles in regulating maintenance, expansion, and differentiation of hPSCs. In addition to its regulatory functions in hematopoiesis and blood-related disorders, the transcription factor RUNX1 is also required for the formation of definitive blood stem cells. In this study, we demonstrated that expression of endogenous RUNX1a, an isoform of RUNX1, parallels with lineage commitment and hematopoietic emergence from hPSCs, including both human embryonic stem cells and inducible pluripotent stem cells. In a defined hematopoietic differentiation system, ectopic expression of RUNX1a facilitates emergence of hematopoietic progenitor cells (HPCs) and positively regulates expression of mesoderm and hematopoietic differentiation-related factors, including Brachyury, KDR, SCL, GATA2, and PU.1. HPCs derived from RUNX1a hPSCs show enhanced expansion ability, and the ex vivo–expanded cells are capable of differentiating into multiple lineages. Expression of RUNX1a in embryoid bodies (EBs) promotes definitive hematopoiesis that generates erythrocytes with β-globin production. Moreover, HPCs generated from RUNX1a EBs possess ≥9-week repopulation ability and show multilineage hematopoietic reconstitution in vivo. Together, our results suggest that RUNX1a facilitates the process of producing therapeutic HPCs from hPSCs.

scholarly journals OP9 Stroma Augments Survival of Hematopoietic Precursors and Progenitors During Hematopoietic Differentiation from Human Embryonic Stem Cells

Stem Cells ◽  
2008 ◽  
Vol 26 (12) ◽  
pp. 3267-3267
Author(s):  
Junfeng Ji ◽  
Kausalia Vijayaragavan ◽  
Marc Bosse ◽  
Pablo Menendez ◽  
Katja Weisel ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Human Embryonic Stem Cells ◽  
Embryonic Stem ◽  
Hematopoietic Differentiation

scholarly journals Dysregulated Gene Expression During Hematopoietic Differentiation From Human Embryonic Stem Cells

2011 ◽  
Vol 19 (4) ◽  
pp. 768-781 ◽  
Author(s):  
Gautam Dravid ◽  
Yuhua Zhu ◽  
Jessica Scholes ◽  
Denis Evseenko ◽  
Gay M Crooks
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Human Embryonic Stem Cells ◽  
Embryonic Stem ◽  
Hematopoietic Differentiation

Hematopoietic Differentiation of Human Embryonic Stem Cells in Vitro : Comparison of Three Cell Lines

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4787-4787
Author(s):  
Marion Brenot ◽  
Annelise Bennaceur-Griscelli ◽  
Marc Peschanski ◽  
Maria Teresa Mitjavila-Garcia
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Cell Lines ◽  
Human Embryonic Stem Cells ◽  
Hematopoietic Cells ◽  
Embryonic Stem ◽  
Embryoid Bodies ◽  
Hematopoietic Differentiation ◽  
Hematopoietic Stem

Abstract Human embryonic stem cells (hES) isolated from the inner cell mass of a blastocyst have the ability to self renew indefinitely while maintaining their pluripotency to differentiate into multiple cell lineages. Therefore, hES represent an important source of cells for perspective cell therapies and serve as an essential tool for fundamental research, specifically for understanding pathophysiological mechanisms of human diseases for the development of novel pharmacological drugs. The generation of hematopoietic stem cells from hES may serve as an alternative source of cells for hematopoietic reconstitution following bone marrow transplantation and an interesting approach to understand early stages of hematopoietic development which are difficult to study in human embryos. Using two different methods, we have differentiated three hES cell lines (SA01, H1 and H9) into hematopoietic cells by generating embryoid bodies and co-culturing on the murine Op9 cell line. In both experimental approaches, we obtain cells expressing CD34 and when cultured in hematopoietic conditions, SA01 and H1 cell lines differentiate into various hematopoietic lineages as demonstrated by BFU-E, CFU-GM and CFU-GEMM colony formation, whereas H9 have almost exclusively granulo-macrophage differentiation. Cells composing these hematopoietic colonies express CD45, CD11b, CD31, CD41 and CD235 and staining with May Grundwald-Giemsa demonstrate neutrophil and erythrocyte morphology. These results demonstrate the capacity of hES to differentiate into mature hematopoietic cells in vitro. Nevertheless, there exist some quantitative and qualitative differences about hematopoietic differentiation between the hES cell lines used. However, we still have to evaluate their capacity to reconstitute hematopoiesis in vivo in an immune deficient mouse model. We will also be interested in developing in vitro methods to expand these hematopoietic precursor cells derived from hES which may be used as a viable source for future cell therapy.

scholarly journals Regulated expression of microRNAs-126/126* inhibits erythropoiesis from human embryonic stem cells

Blood ◽  
2011 ◽  
Vol 117 (7) ◽  
pp. 2157-2165 ◽  
Author(s):  
Xinqiang Huang ◽  
Eric Gschweng ◽  
Ben Van Handel ◽  
Donghui Cheng ◽  
Hanna K. A. Mikkola ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Human Embryonic Stem Cells ◽  
Protein Tyrosine Phosphatase ◽  
Embryoid Body ◽  
Tyrosine Phosphatase ◽  
Embryonic Stem ◽  
Hematopoietic Differentiation ◽  
Protein Tyrosine

Abstract MicroRNAs (miRs) play an important role in cell differentiation and maintenance of cell identity, but relatively little is known of their functional role in modulating human hematopoietic lineage differentiation. Human embryonic stem cells (hESCs) provide a model system to study early human hematopoiesis. We differentiated hESCs by embryoid body (EB) formation and compared the miR expression profile of undifferentiated hESCs to CD34+ EB cells. miRs-126/126* were the most enriched of the 7 miRs that were up-regulated in CD34+ cells, and their expression paralleled the kinetics of hematopoietic transcription factors RUNX1, SCL, and PU.1. To define the role of miRs-126/126* in hematopoiesis, we created hESCs overexpressing doxycycline-regulated miRs-126/126* and analyzed their hematopoietic differentiation. Induction of miRs-126/126* during both EB differentiation and colony formation reduced the number of erythroid colonies, suggesting an inhibitory role of miRs-126/126* in erythropoiesis. Protein tyrosine phosphatase, nonreceptor type 9 (PTPN9), a protein tyrosine phosphatase that is required for growth and expansion of erythroid cells, is one target of miR-126. PTPN9 restoration partially relieved the suppressed erythropoiesis caused by miRs-126/126*. Our results define an important function of miRs-126/126* in negative regulation of erythropoiesis, providing the first evidence for a role of miR in hematopoietic differentiation of hESCs.

scholarly journals Hematopoietic differentiation of human embryonic stem cells progresses through sequential hematoendothelial, primitive, and definitive stages resembling human yolk sac development

Blood ◽  
2005 ◽  
Vol 106 (3) ◽  
pp. 860-870 ◽  
Author(s):  
Elias T. Zambidis ◽  
Bruno Peault ◽  
Tea Soon Park ◽  
Fred Bunz ◽  
Curt I. Civin
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Human Embryonic Stem Cells ◽  
Embryonic Stem ◽  
Homeobox Gene ◽  
Fetal Hemoglobin ◽  
Yolk Sac ◽  
Embryoid Bodies ◽  
Hematopoietic Differentiation ◽  
Hematopoietic Stem

AbstractWe elucidate the cellular and molecular kinetics of the stepwise differentiation of human embryonic stem cells (hESCs) to primitive and definitive erythromyelopoiesis from human embryoid bodies (hEBs) in serum-free clonogenic assays. Hematopoiesis initiates from CD45 hEB cells with emergence of semiadherent mesodermal-hematoendothelial (MHE) colonies that can generate endothelium and form organized, yolk sac–like structures that secondarily generate multipotent primitive hematopoietic stem progenitor cells (HSPCs), erythroblasts, and CD13+CD45+ macrophages. A first wave of hematopoiesis follows MHE colony emergence and is predominated by primitive erythropoiesis characterized by a brilliant red hemoglobinization, CD71/CD325a (glycophorin A) expression, and exclusively embryonic/fetal hemoglobin expression. A second wave of definitive-type erythroid burst-forming units (BFU-e's), erythroid colony-forming units (CFU-e's), granulocyte-macrophage colony-forming cells (GM-CFCs), and multilineage CFCs follows next from hEB progenitors. These stages of hematopoiesis proceed spontaneously from hEB-derived cells without requirement for supplemental growth factors during hEB differentiation. Gene expression analysis of differentiating hEBs revealed that initiation of hematopoiesis correlated with increased levels of SCL/TAL1, GATA1, GATA2, CD34, CD31, and the homeobox gene-regulating factor CDX4 These data indicate that hematopoietic differentiation of hESCs models the earliest events of embryonic and definitive hematopoiesis in a manner resembling human yolk sac development, thus providing a valuable tool for dissecting the earliest events in human HSPC genesis.

scholarly journals MEIS2 regulates endothelial to hematopoietic transition of human embryonic stem cells by targeting TAL1

2018 ◽  
Vol 9 (1) ◽  
Author(s):  
Mengge Wang ◽  
Hongtao Wang ◽  
Yuqi Wen ◽  
Xiaoyuan Chen ◽  
Xin Liu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Human Embryonic Stem Cells ◽  
Blood Cells ◽  
Integration Site ◽  
Embryonic Stem ◽  
Gene Profiling ◽  
Hematopoietic Differentiation ◽  
Hematopoietic Stem ◽  
Megakaryocytic Differentiation

Abstract Background Despite considerable progress in the development of methods for hematopoietic differentiation, efficient generation of transplantable hematopoietic stem cells (HSCs) and other genuine functional blood cells from human embryonic stem cells (hESCs) is still unsuccessful. Therefore, a better understanding of the molecular mechanism underlying hematopoietic differentiation of hESCs is highly demanded. Methods In this study, by using whole-genome gene profiling, we identified Myeloid Ectopic Viral Integration Site 2 homolog (MEIS2) as a potential regulator of hESC early hematopoietic differentiation. We deleted MEIS2 gene in hESCs using the CRISPR/CAS9 technology and induced them to hematopoietic differentiation, megakaryocytic differentiation. Results In this study, we found that MEIS2 deletion impairs early hematopoietic differentiation from hESCs. Furthermore, MEIS2 deletion suppresses hemogenic endothelial specification and endothelial to hematopoietic transition (EHT), leading to the impairment of hematopoietic differentiation. Mechanistically, TAL1 acts as a downstream gene mediating the function of MEIS2 during early hematopoiesis. Interestingly, unlike MEIS1, MEIS2 deletion exerts minimal effects on megakaryocytic differentiation and platelet generation from hESCs. Conclusions Our findings advance the understanding of human hematopoietic development and may provide new insights for large-scale generation of functional blood cells for clinical applications.

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