title: Runx1 is essential for hematopoietic commitment at the hemangioblast stage of development in vitro.
abstract: In this report we demonstrate a role for Runx1 (AML1) at the hemangioblast stage of hematopoietic and endothelial development in embryonic stem (ES) cell-derived embryoid bodies (EBs). Runx1 is expressed in EBs during the appearance of precursors with hemangioblast properties, the blast colony-forming cells (BL-CFCs). Cell sorting studies revealed that all BL-CFCs within EBs express Runx1. Runx1-deficient EBs consistently generate 10- to 20-fold fewer blast colonies than wild-type controls and display a complete block in definitive hematopoiesis. Despite this defect, Runx1-/- EBs and yolk sacs from mutant embryos generate normal numbers of primitive erythroid precursors. These observations clearly demonstrate that Runx1 functions early in hematopoietic development, and they support the interpretation that the primitive erythroid lineage is established early by a subset of BL-CFCs that develop in a Runx1-independent fashion.
authors.affiliation: Carl C. Icahn Institute for Gene Therapy and Molecular Medicine, Mount Sinai School of Medicine, New York, NY, USA.
authors.forename: Georges
authors.initials: G
authors.lastname: Lacaud
authors.forename: Lia
authors.initials: L
authors.lastname: Gore
authors.forename: Marion
authors.initials: M
authors.lastname: Kennedy
authors.forename: Valerie
authors.initials: V
authors.lastname: Kouskoff
authors.forename: Paul
authors.initials: P
authors.lastname: Kingsley
authors.forename: Christopher
authors.initials: C
authors.lastname: Hogan
authors.forename: Leif
authors.initials: L
authors.lastname: Carlsson
authors.forename: Nancy
authors.initials: N
authors.lastname: Speck
authors.forename: James
authors.initials: J
authors.lastname: Palis
authors.forename: Gordon
authors.initials: G
authors.lastname: Keller
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D050676:Core Binding Factor Alpha 2 Subunit; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D004622:Embryo, Mammalian / Q000166:cytology* / Q000196:embryology / Q000378:metabolism; D004920:Erythropoiesis / Q000187:drug effects; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D006410:Hematopoiesis / Q000187:drug effects*; D006412:Hematopoietic Stem Cells / Q000378:metabolism; D051379:Mice; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger / Q000032:analysis; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015017:Yolk Sac / Q000166:cytology
chemical_list: D050676:Core Binding Factor Alpha 2 Subunit; D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; C493726:Runx1 protein, mouse; D014157:Transcription Factors