title: Circulation-independent differentiation pathway from extraembryonic mesoderm toward hematopoietic stem cells via hemogenic angioblasts.
abstract: A large gap exists in our understanding of the course of differentiation from mesoderm to definitive hematopoietic stem cells (HSCs). Previously, we reported that Runx1(+) cells in embryonic day 7.5 (E7.5) embryos contribute to the hemogenic endothelium in the E10.5 aorta-gonad-mesonephros (AGM) region and HSCs in the adult bone marrow. Here, we show that two Runx1(+) populations subdivided by Gata1 expression exist in E7.5 embryos. The hemogenic endothelium and the HSCs are derived only from the Runx1(+)Gata1(-) population. A subset of this population moves from the extra- to intraembryonic region during E7.5-E8.0, where it contributes to the hemogenic endothelium of the dorsal aorta (DA). Migration occurs before the heartbeat is initiated, and it is independent of circulation. This suggests a developmental trajectory from Runx1(+) cells in the E7.5 extraembryonic region to definitive HSCs via the hemogenic endothelium.
authors: Laboratory of Stem Cell Biology, Center for Developmental Biology, RIKEN Kobe, 2-2-3 Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan; Department of Haematology, Wellcome Trust-MRC Cambridge Stem Cell Institute, University of Cambridge, Hills Road, Cambridge CB2 0XY, UK. Electronic address: yt305@cam.ac.uk.
authors: Yosuke
authors: Y
authors: Tanaka
authors: Rosalind and Morris Goodman Cancer Research Centre, Department of Human Genetics, McGill University, Montreal, QC H3A 1A3, Canada.
authors: Veronica
authors: V
authors: Sanchez
authors: Organogenesis and Neurogenesis Group, Center for Developmental Biology, RIKEN Kobe, 2-2-3 Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan.
authors: Nozomu
authors: N
authors: Takata
authors: Department of Hematology, Juntendo University School of Medicine, 2-1-2 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.
authors: Tomomasa
authors: T
authors: Yokomizo
authors: Rosalind and Morris Goodman Cancer Research Centre, Department of Human Genetics, McGill University, Montreal, QC H3A 1A3, Canada.
authors: Yojiro
authors: Y
authors: Yamanaka
authors: Laboratory of Stem Cell Biology, Center for Developmental Biology, RIKEN Kobe, 2-2-3 Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan.
authors: Hiroshi
authors: H
authors: Kataoka
authors: Department of Biosystems Science and Engineering, ETH Zurich, 4058 Basel, Switzerland.
authors: Philipp S
authors: PS
authors: Hoppe
authors: Department of Biosystems Science and Engineering, ETH Zurich, 4058 Basel, Switzerland.
authors: Timm
authors: T
authors: Schroeder
authors: Laboratory of Stem Cell Biology, Center for Developmental Biology, RIKEN Kobe, 2-2-3 Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan.
authors: Shin-Ichi
authors: S
authors: Nishikawa
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D019070:Cell Lineage; D002465:Cell Movement; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics / Q000378:metabolism; D050982:GATA1 Transcription Factor / Q000235:genetics / Q000378:metabolism; D055018:Hemangioblasts / Q000166:cytology / Q000378:metabolism*; D008648:Mesoderm / Q000166:cytology* / Q000196:embryology / Q000378:metabolism; D051379:Mice
chemical_list: D050676:Core Binding Factor Alpha 2 Subunit; D050982:GATA1 Transcription Factor; C494689:Gata1 protein, mouse; C493726:Runx1 protein, mouse