To search for genes that promote hematopoietic development from human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs), we overexpressed several known hematopoietic regulator genes in hESC/iPSC-derived CD34+CD43+ endothelial cells (ECs) enriched in hemogenic endothelium (HE). Among the genes tested, only Sox17, a gene encoding a transcription factor of the SOX family, promoted cell growth and supported expansion of CD34+CD43+CD45-/low cells expressing the HE marker VE-cadherin. SOX17 was expressed at high levels in CD34+CD43- ECs compared with low levels in CD34 +CD43+CD45+ pre-hematopoietic progenitor cells (pre-HPCs) and CD34+CD43+CD45+ HPCs. Sox17-overexpressing cells formed semiadherent cell aggregates and generated few hematopoietic progenies. However, they retained hemogenic potential and gave rise to hematopoietic progenies on inactivation of Sox17. Global gene-expression analyses revealed that the CD34+CD43+CD45-/low cells expanded on overexpression of Sox17 are HE-like cells developmentally placed between ECs and pre-HPCs. Sox17 overexpression also reprogrammed both pre-HPCs and HPCs into HE-like cells. Genome-wide mapping of Sox17-binding sites revealed that Sox17 activates the transcription of key regulator genes for vasculogenesis, hematopoiesis, and erythrocyte differentiation directly. Depletion of SOX17 in CD34+CD43- ECs severely compromised their hemogenic activity. These findings suggest that SOX17 plays a key role in priming hemogenic potential in ECs, thereby regulating hematopoietic development from hESCs/iPSCs. © 2013 by The American Society of Hematology.
CITATION STYLE
Nakajima-Takagi, Y., Osawa, M., Oshima, M., Takagi, H., Miyagi, S., Endoh, M., … Iwama, A. (2013). Role of SOX17 in hematopoietic development from human embryonic stem cells. Blood, 121(3), 447–458. https://doi.org/10.1182/blood-2012-05-431403
Mendeley helps you to discover research relevant for your work.