title: Erythroid/myeloid progenitors and hematopoietic stem cells originate from distinct populations of endothelial cells.
abstract: Hematopoietic stem cells (HSCs) and an earlier wave of definitive erythroid/myeloid progenitors (EMPs) differentiate from hemogenic endothelial cells in the conceptus. EMPs can be generated in vitro from embryonic or induced pluripotent stem cells, but efforts to produce HSCs have largely failed. The formation of both EMPs and HSCs requires the transcription factor Runx1 and its non-DNA binding partner core binding factor β (CBFβ). Here we show that the requirements for CBFβ in EMP and HSC formation in the conceptus are temporally and spatially distinct. Panendothelial expression of CBFβ in Tek-expressing cells was sufficient for EMP formation, but was not adequate for HSC formation. Expression of CBFβ in Ly6a-expressing cells, on the other hand, was sufficient for HSC, but not EMP, formation. The data indicate that EMPs and HSCs differentiate from distinct populations of hemogenic endothelial cells, with Ly6a expression specifically marking the HSC-generating hemogenic endothelium.
authors.affiliation: Abramson Family Cancer Research Institute and Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Chen
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Maria Elena
authors.initials: ME
authors.lastname: De Obaldia
authors.forename: Qi
authors.initials: Q
authors.lastname: Yang
authors.forename: Amanda D
authors.initials: AD
authors.lastname: Yzaguirre
authors.forename: Tomoko
authors.initials: T
authors.lastname: Yamada-Inagawa
authors.forename: Chris S
authors.initials: CS
authors.lastname: Vink
authors.forename: Avinash
authors.initials: A
authors.lastname: Bhandoola
authors.forename: Elaine
authors.initials: E
authors.lastname: Dzierzak
authors.forename: Nancy A
authors.initials: NA
authors.lastname: Speck
mesh_terms: D000818:Animals; D000950:Antigens, Ly / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D019070:Cell Lineage; D002478:Cells, Cultured; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics / Q000378:metabolism; D050658:Core Binding Factor beta Subunit / Q000235:genetics / Q000378:metabolism*; D004622:Embryo, Mammalian / Q000166:cytology / Q000502:physiology; D042783:Endothelial Cells / Q000166:cytology / Q000502:physiology*; D041905:Erythroid Cells / Q000166:cytology / Q000378:metabolism*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000502:physiology*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D022423:Myeloid Cells / Q000166:cytology / Q000502:physiology*; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D042787:Receptor, TIE-2; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D019076:Transgenes
chemical_list: D000950:Antigens, Ly; C493693:Cbfb protein, mouse; D050676:Core Binding Factor Alpha 2 Subunit; D050658:Core Binding Factor beta Subunit; C074650:Ly6a protein, mouse; D008565:Membrane Proteins; D011993:Recombinant Fusion Proteins; D020794:Receptor Protein-Tyrosine Kinases; D042787:Receptor, TIE-2; C079086:Tek protein, mouse