Identification of the hemogenic endothelial progenitor and its direct precursor in human pluripotent stem cell differentiation cultures
| Autor: | Akhilesh Kumar, Mitchell D. Probasco, Kran Suknuntha, Maxim A. Vodyanik, Padma Priya Togarrati, Shulan Tian, Kyung Dal Choi, Igor I. Slukvin, Fnu Samarjeet, James A. Thomson, Ron Stewart |
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| Rok vydání: | 2011 |
| Předmět: |
Pluripotent Stem Cells
Hemangioblasts Cellular differentiation Biology General Biochemistry Genetics and Molecular Biology Article Cell Line 03 medical and health sciences 0302 clinical medicine Antigens CD Humans Progenitor cell 10. No inequality Induced pluripotent stem cell lcsh:QH301-705.5 030304 developmental biology Hemogenic endothelium 0303 health sciences Cell Differentiation Cadherins Hematopoietic Stem Cells Cell biology Endothelial stem cell Haematopoiesis lcsh:Biology (General) 030220 oncology & carcinogenesis Hemangioblast Fibroblast Growth Factor 2 Stem cell |
| Zdroj: | Cell Reports, Vol 2, Iss 3, Pp 553-567 (2012) |
| ISSN: | 2211-1247 |
| Popis: | Hemogenic endothelium (HE) has been recognized as a source of hematopoietic stem cells (HSCs) in the embryo. Access to human HE progenitors (HEPs) is essential for enabling the investigation of the molecular determinants of HSC specification. Here, we show that HEPs capable of generating definitive hematopoietic cells can be obtained from human pluripotent stem cells (hPSCs) and identified precisely by a VE-cadherin(+)CD73(-)CD235a/CD43(-) phenotype. This phenotype discriminates true HEPs from VE-cadherin(+)CD73(+) non-HEPs and VE-cadherin(+)CD235a(+)CD41a(-) early hematopoietic cells with endothelial and FGF2-dependent hematopoietic colony-forming potential. We found that HEPs arise at the post-primitive-streak stage of differentiation directly from VE-cadherin-negative KDR(bright)APLNR(+)PDGFRα(low/-) hematovascular mesodermal precursors (HVMPs). In contrast, hemangioblasts, which are capable of forming endothelium and primitive blood cells, originate from more immature APLNR(+)PDGFRα(+) mesoderm. The demarcation of HEPs and HVMPs provides a platform for modeling blood development from endothelium with a goal of facilitating the generation of HSCs from hPSCs. |
| Databáze: | OpenAIRE |
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