title: Direct induction of haematoendothelial programs in human pluripotent stem cells by transcriptional regulators.
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.
authors.affiliation: National Primate Research Center, University of Wisconsin Graduate School, 1220 Capitol Court, Madison, Wisconsin 53715, USA.
authors.forename: Irina
authors.initials: I
authors.lastname: Elcheva
authors.affiliation: National Primate Research Center, University of Wisconsin Graduate School, 1220 Capitol Court, Madison, Wisconsin 53715, USA.
authors.forename: Vera
authors.initials: V
authors.lastname: Brok-Volchanskaya
authors.affiliation: National Primate Research Center, University of Wisconsin Graduate School, 1220 Capitol Court, Madison, Wisconsin 53715, USA.
authors.forename: Akhilesh
authors.initials: A
authors.lastname: Kumar
authors.affiliation: National Primate Research Center, University of Wisconsin Graduate School, 1220 Capitol Court, Madison, Wisconsin 53715, USA.
authors.forename: Patricia
authors.initials: P
authors.lastname: Liu
authors.affiliation: National Primate Research Center, University of Wisconsin Graduate School, 1220 Capitol Court, Madison, Wisconsin 53715, USA.
authors.forename: Jeong-Hee
authors.initials: JH
authors.lastname: Lee
authors.affiliation: National Primate Research Center, University of Wisconsin Graduate School, 1220 Capitol Court, Madison, Wisconsin 53715, USA.
authors.forename: Lilian
authors.initials: L
authors.lastname: Tong
authors.affiliation: National Primate Research Center, University of Wisconsin Graduate School, 1220 Capitol Court, Madison, Wisconsin 53715, USA.
authors.forename: Maxim
authors.initials: M
authors.lastname: Vodyanik
authors.affiliation: Morgridge Institute for Research, 330 N. Orchard Street, Madison, Wisconsin 53715, USA.
authors.forename: Scott
authors.initials: S
authors.lastname: Swanson
authors.affiliation: Morgridge Institute for Research, 330 N. Orchard Street, Madison, Wisconsin 53715, USA.
authors.forename: Ron
authors.initials: R
authors.lastname: Stewart
authors.affiliation: Lillehei Heart Institute, University of Minnesota, Minneapolis, Minnesota 55455, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Kyba
authors.affiliation: Center for Cardiovascular Regeneration, Department of Cardiovascular Sciences, Houston Methodist Research Institute, Houston, Texas 77030, USA.
authors.forename: Eduard
authors.initials: E
authors.lastname: Yakubov
authors.affiliation: Center for Cardiovascular Regeneration, Department of Cardiovascular Sciences, Houston Methodist Research Institute, Houston, Texas 77030, USA.
authors.forename: John
authors.initials: J
authors.lastname: Cooke
authors.affiliation: 1] Morgridge Institute for Research, 330 N. Orchard Street, Madison, Wisconsin 53715, USA [2] Department of Cell and Regenerative Biology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin 53707-7365, USA [3] Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, California 93106, USA.
authors.forename: James A
authors.initials: JA
authors.lastname: Thomson
authors.affiliation: 1] National Primate Research Center, University of Wisconsin Graduate School, 1220 Capitol Court, Madison, Wisconsin 53715, USA [2] Department of Cell and Regenerative Biology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin 53707-7365, USA [3] Department of Pathology and Laboratory Medicine, University of Wisconsin Medical School, 600 Highland Avenue, Madison, Wisconsin 53792, USA.
authors.forename: Igor
authors.initials: I
authors.lastname: Slukvin
mesh_terms: D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D005786:Gene Expression Regulation; D006410:Hematopoiesis / Q000502:physiology; D006801:Humans; D051379:Mice; D039904:Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D014157:Transcription Factors