Direct induction of haematoendothelial programs in human pluripotent stem cells by transcriptional regulators

Irina Elcheva, Vera Brok-Volchanskaya, Akhilesh Kumar, Patricia Liu, Jeong-Hee Lee, Lilian Tong, Maxim Vodyanik, Scott Swanson, Ron Stewart, Michael Kyba, Eduard Yakubov, John Cooke, James A. Thomson and Igor Slukvin ()
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Irina Elcheva: National Primate Research Center, University of Wisconsin Graduate School
Vera Brok-Volchanskaya: National Primate Research Center, University of Wisconsin Graduate School
Akhilesh Kumar: National Primate Research Center, University of Wisconsin Graduate School
Patricia Liu: National Primate Research Center, University of Wisconsin Graduate School
Jeong-Hee Lee: National Primate Research Center, University of Wisconsin Graduate School
Lilian Tong: National Primate Research Center, University of Wisconsin Graduate School
Maxim Vodyanik: National Primate Research Center, University of Wisconsin Graduate School
Scott Swanson: Morgridge Institute for Research
Ron Stewart: Morgridge Institute for Research
Michael Kyba: Lillehei Heart Institute, University of Minnesota
Eduard Yakubov: Center for Cardiovascular Regeneration, Houston Methodist Research Institute
John Cooke: Center for Cardiovascular Regeneration, Houston Methodist Research Institute
James A. Thomson: Morgridge Institute for Research
Igor Slukvin: National Primate Research Center, University of Wisconsin Graduate School

Nature Communications, 2014, vol. 5, issue 1, 1-11

Abstract: Abstract Advancing pluripotent stem cell technologies for modelling haematopoietic stem cell development and blood therapies requires identifying key regulators of haematopoietic commitment from human pluripotent stem cells (hPSCs). Here, by screening the effect of 27 candidate factors, we reveal two groups of transcriptional regulators capable of inducing distinct haematopoietic programs from hPSCs: pan-myeloid (ETV2 and GATA2) and erythro-megakaryocytic (GATA2 and TAL1). In both cases, these transcription factors directly convert hPSCs to endothelium, which subsequently transform into blood cells with pan-myeloid or erythro-megakaryocytic potential. These data demonstrate that two distinct genetic programs regulate the haematopoietic development from hPSCs and that both of these programs specify hPSCs directly to haemogenic endothelial cells. In addition, this study provides a novel method for the efficient induction of blood and endothelial cells from hPSCs via the overexpression of modified mRNA for the selected transcription factors.

Date: 2014
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DOI: 10.1038/ncomms5372

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