title: Early ontogenic origin of the hematopoietic stem cell lineage.
abstract: Several lines of evidence suggest that the adult hematopoietic system has multiple developmental origins, but the ontogenic relationship between nascent hematopoietic populations under this scheme is poorly understood. In an alternative theory, the earliest definitive blood precursors arise from a single anatomical location, which constitutes the cellular source for subsequent hematopoietic populations. To deconvolute hematopoietic ontogeny, we designed an embryo-rescue system in which the key hematopoietic factor Runx1 is reactivated in Runx1-null conceptuses at specific developmental stages. Using complementary in vivo and ex vivo approaches, we provide evidence that definitive hematopoiesis and adult-type hematopoietic stem cells originate predominantly in the nascent extraembryonic mesoderm. Our data also suggest that other anatomical sites that have been proposed to be sources of the definitive hematopoietic hierarchy are unlikely to play a substantial role in de novo blood generation.
authors.affiliation: Laboratory for Stem Cell Biology, and Laboratory for Early Embryogenesis, Center for Developmental Biology,  RIKEN Kobe Institute, Kobe, Hyogo 650-0047,  Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Misato
authors.initials: M
authors.lastname: Hayashi
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Kubota
authors.forename: Hiroki
authors.initials: H
authors.lastname: Nagai
authors.forename: Guojun
authors.initials: G
authors.lastname: Sheng
authors.forename: Shin-Ichi
authors.initials: S
authors.lastname: Nishikawa
authors.forename: Igor M
authors.initials: IM
authors.lastname: Samokhvalov
mesh_terms: D000483:Alleles; D000818:Animals; D019070:Cell Lineage; D050676:Core Binding Factor Alpha 2 Subunit; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D018507:Gene Expression Regulation, Developmental; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D017403:In Situ Hybridization; D051379:Mice; D008810:Mice, Inbred C57BL; D008957:Models, Genetic; D013997:Time Factors; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: D050676:Core Binding Factor Alpha 2 Subunit; C493726:Runx1 protein, mouse; D001616:beta-Galactosidase