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

• Published in: Nature communications Vol. 5; no. 1; p. 4372
• Main Authors: Elcheva, Irina, Brok-Volchanskaya, Vera, Kumar, Akhilesh, Liu, Patricia, Lee, Jeong-Hee, Tong, Lilian, Vodyanik, Maxim, Swanson, Scott, Stewart, Ron, Kyba, Michael, Yakubov, Eduard, Cooke, John, Thomson, James A., Slukvin, Igor
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 14.07.2014; Nature Publishing Group
• Subjects: 13/100; 13/109; 13/31; 13/51; 14/19; 38/39; 38/90; 42/44; 631/136/232; 631/136/532/2064; 631/45/612/822; Animals; Cell Line; Cells, Cultured; Endothelial Cells - cytology; Endothelial Cells - metabolism; Gene Expression Regulation; Hematopoiesis - physiology; Humanities and Social Sciences; Humans; Mice; multidisciplinary; Pluripotent Stem Cells - cytology; Pluripotent Stem Cells - metabolism; Science; Science (multidisciplinary); Transcription Factors - metabolism
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms5372

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. The haemogenic endothelium gives rise to haematopoietic cells including haematopoietic stem cells. Here, the authors show that the transduction of two combinations of transcription factors into human pluripotent stem cells convert these into haemogenic endothelial cells with distinct lineage potentials.