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; Igor Slukvin

doi:10.1038/ncomms5372

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, Igor Slukvin

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141 Scopus citations

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.

Original language	English (US)
Article number	4372
Journal	Nature communications
Volume	5
DOIs	https://doi.org/10.1038/ncomms5372 https://doi.org/10.1038/ncomms5372
State	Published - Jul 14 2014

Bibliographical note

Funding Information:
We thank Mitchell Probasco for cell sorting and Matt Raymond for editorial assistance. This work was supported by funds from the National Institute of Health (U01HL099773, U01HL100407, U01HL099997 and P51 RR000167) and The Charlotte Geyer Foundation.

Keywords

Animals
Cell Line
Cells, Cultured
Endothelial Cells/cytology
Gene Expression Regulation
Hematopoiesis/physiology
Humans
Mice
Pluripotent Stem Cells/cytology
Transcription Factors/metabolism

PubMed: MeSH publication types

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

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Elcheva, I., Brok-Volchanskaya, V., Kumar, A., Liu, P., Lee, J. H., Tong, L., Vodyanik, M., Swanson, S., Stewart, R., Kyba, M., Yakubov, E., Cooke, J., Thomson, J. A., & Slukvin, I. (2014). Direct induction of haematoendothelial programs in human pluripotent stem cells by transcriptional regulators. Nature communications, 5, Article 4372. https://doi.org/10.1038/ncomms5372, https://doi.org/10.1038/ncomms5372

Elcheva, I, Brok-Volchanskaya, V, Kumar, A, Liu, P, Lee, JH, Tong, L, Vodyanik, M, Swanson, S, Stewart, R, Kyba, M, Yakubov, E, Cooke, J, Thomson, JA & Slukvin, I 2014, 'Direct induction of haematoendothelial programs in human pluripotent stem cells by transcriptional regulators', Nature communications, vol. 5, 4372. https://doi.org/10.1038/ncomms5372, https://doi.org/10.1038/ncomms5372

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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.",

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N2 - 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.

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

Abstract

Bibliographical note

Keywords

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