title: TGFβ inhibition enhances the generation of hematopoietic progenitors from human ES cell-derived hemogenic endothelial cells using a stepwise strategy.
abstract: Embryonic hematopoiesis is a complex process. Elucidating the mechanism regulating hematopoietic differentiation from pluripotent stem cells would allow us to establish a strategy to efficiently generate hematopoietic cells. However, the mechanism governing the generation of hematopoietic progenitors from human embryonic stem cells (hESCs) remains unknown. Here, on the basis of the emergence of CD43(+) hematopoietic cells from hemogenic endothelial (HE) cells, we demonstrated that VEGF was essential and sufficient, and that bFGF was synergistic with VEGF to specify the HE cells and the subsequent transition into CD43(+) hematopoietic cells. Significantly, we identified TGFβ as a novel signal to regulate hematopoietic development, as the TGFβ inhibitor SB 431542 significantly promoted the transition from HE cells into CD43(+) hematopoietic progenitor cells (HPCs) during hESC differentiation. By defining these critical signaling factors during hematopoietic differentiation, we can efficiently generate HPCs from hESCs. Our strategy could offer an in vitro model to study early human hematopoietic development.
authors.affiliation: Department of Cell Biology, The MOE Key Laboratory of Cell Proliferation and Differentiation, College of Life Sciences, Peking University, Beijing, China.
authors.forename: Chengyan
authors.initials: C
authors.lastname: Wang
authors.forename: Xuming
authors.initials: X
authors.lastname: Tang
authors.forename: Xiaomeng
authors.initials: X
authors.lastname: Sun
authors.forename: Zhenchuan
authors.initials: Z
authors.lastname: Miao
authors.forename: Yaxin
authors.initials: Y
authors.lastname: Lv
authors.forename: Yanlei
authors.initials: Y
authors.lastname: Yang
authors.forename: Huidan
authors.initials: H
authors.lastname: Zhang
authors.forename: Pengbo
authors.initials: P
authors.lastname: Zhang
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.forename: Liying
authors.initials: L
authors.lastname: Du
authors.forename: Yang
authors.initials: Y
authors.lastname: Gao
authors.forename: Ming
authors.initials: M
authors.lastname: Yin
authors.forename: Mingxiao
authors.initials: M
authors.lastname: Ding
authors.forename: Hongkui
authors.initials: H
authors.lastname: Deng
mesh_terms: D028341:Activins / Q000494:pharmacology; D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D002454:Cell Differentiation; D002460:Cell Line; D049109:Cell Proliferation; D004149:Dioxoles / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005346:Fibroblast Growth Factors / Q000494:pharmacology; D005434:Flow Cytometry; D055018:Hemangioblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D051917:Leukosialin / Q000378:metabolism; D008648:Mesoderm / Q000166:cytology / Q000378:metabolism; D051379:Mice; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors* / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology
chemical_list: C459179:4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide; D001549:Benzamides; D004149:Dioxoles; D051917:Leukosialin; C465014:SPN protein, human; D016212:Transforming Growth Factor beta; D042461:Vascular Endothelial Growth Factor A; C422405:activin A; D028341:Activins; D005346:Fibroblast Growth Factors