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 ◽  
...  

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.

1996 ◽  
Vol 91 (2) ◽  
pp. 304-307 ◽  
Author(s):  
Wouter G. van Inzen ◽  
Maikel P. Peppelenbosch ◽  
Maria W.M. van den Brand ◽  
Leon G.J. Tertoolen ◽  
Siegfried de Laat

2016 ◽  
Vol 425 (1-2) ◽  
pp. 95-102
Author(s):  
Zahra Shokati Eshkiki ◽  
Mohammad Hossein Ghahremani ◽  
Parisa Shabani ◽  
Sattar Gorgani Firuzjaee ◽  
Asie Sadeghi ◽  
...  

Blood ◽  
2003 ◽  
Vol 102 (3) ◽  
pp. 906-915 ◽  
Author(s):  
Kristin Chadwick ◽  
Lisheng Wang ◽  
Li Li ◽  
Pablo Menendez ◽  
Barbara Murdoch ◽  
...  

Abstract Human embryonic stem cells (hESCs) randomly differentiate into multiple cell types during embryoid body (EB) development. To date, characterization of specific factors capable of influencing hematopoietic cell fate from hESCs remains elusive. Here, we report that the treatment of hESCs during EB development with a combination of cytokines and bone morphogenetic protein-4 (BMP-4), a ventral mesoderm inducer, strongly promotes hematopoietic differentiation. Hematopoietic progenitors of multiple lineages were generated from EBs and were found to be restricted to the population of progeny expressing cell surface CD45. Addition of BMP-4 had no statistically significant effect on hematopoietic differentiation but enabled significant enhancement in progenitor self-renewal, independent of cytokine treatment. Hematopoietic commitment was characterized as the temporal emergence of single CD45+ cells first detectable after day 10 of culture and was accompanied by expression of hematopoietic transcription factors. Despite the removal of cytokines at day 10, hematopoietic differentiation of hESCs continued, suggesting that cytokines act on hematopoietic precursors as opposed to differentiated hematopoietic cells. Our study establishes the first evidence for the role of cytokines and BMP-4 in promoting hematopoietic differentiation of hESC lines and provides an unprecedented system to study early developmental events that govern the initiation of hematopoiesis in the human.


2016 ◽  
Vol 24 ◽  
pp. S92-S93
Author(s):  
Hiroshi Kohara ◽  
Jiyuan Liao ◽  
Shohei Miyamoto ◽  
Yoko Nagai ◽  
Tomotoshi Marumoto ◽  
...  

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