PMID- 21163928 OWN - NLM STAT- MEDLINE DCOM- 20110331 LR - 20211020 IS - 1528-0020 (Electronic) IS - 0006-4971 (Print) IS - 0006-4971 (Linking) VI - 117 IP - 7 DP - 2011 Feb 17 TI - Regulated expression of microRNAs-126/126* inhibits erythropoiesis from human embryonic stem cells. PG - 2157-65 LID - 10.1182/blood-2010-08-302711 [doi] AB - 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. FAU - Huang, Xinqiang AU - Huang X AD - Howard Hughes Medical Institute, Los Angeles, CA, USA. FAU - Gschweng, Eric AU - Gschweng E FAU - Van Handel, Ben AU - Van Handel B FAU - Cheng, Donghui AU - Cheng D FAU - Mikkola, Hanna K A AU - Mikkola HK FAU - Witte, Owen N AU - Witte ON LA - eng GR - T32 GM007185/GM/NIGMS NIH HHS/United States GR - HHMI/Howard Hughes Medical Institute/United States GR - GM007185/GM/NIGMS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20101216 PL - United States TA - Blood JT - Blood JID - 7603509 RN - 0 (Antigens, CD34) RN - 0 (DNA Primers) RN - 0 (MIRN126 microRNA, human) RN - 0 (MIRN223 microRNA, human) RN - 0 (MicroRNAs) RN - EC 3.1.3.48 (PTPN9 protein, human) RN - EC 3.1.3.48 (Protein Tyrosine Phosphatases, Non-Receptor) SB - IM MH - Antigens, CD34/metabolism MH - Base Sequence MH - Cell Differentiation/genetics/physiology MH - Cell Line MH - Colony-Forming Units Assay MH - DNA Primers/genetics MH - Embryoid Bodies/cytology/metabolism MH - Embryonic Stem Cells/*cytology/*metabolism MH - Erythropoiesis/*genetics/*physiology MH - Gene Expression Regulation, Developmental MH - Humans MH - Kinetics MH - MicroRNAs/*genetics/metabolism MH - Protein Tyrosine Phosphatases, Non-Receptor/genetics/physiology PMC - PMC3062325 EDAT- 2010/12/18 06:00 MHDA- 2011/04/01 06:00 PMCR- 2011/02/17 CRDT- 2010/12/18 06:00 PHST- 2010/12/18 06:00 [entrez] PHST- 2010/12/18 06:00 [pubmed] PHST- 2011/04/01 06:00 [medline] PHST- 2011/02/17 00:00 [pmc-release] AID - S0006-4971(20)55096-9 [pii] AID - 2010/302711 [pii] AID - 10.1182/blood-2010-08-302711 [doi] PST - ppublish SO - Blood. 2011 Feb 17;117(7):2157-65. doi: 10.1182/blood-2010-08-302711. Epub 2010 Dec 16.