Highly potent human hematopoietic stem cells first emerge in the intraembryonic aorta-gonad-mesonephros region

Hematopoietic stem cells (HSCs) emerge during embryogenesis and maintain hematopoiesis in the adult organism. Little is known about the embryonic development of human HSCs. We demonstrate that human HSCs emerge first in the aorta-gonad-mesonephros (AGM) region, specifically in the dorsal aorta, and...

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Veröffentlicht in:The Journal of experimental medicine Jg. 208; H. 12; S. 2417
Hauptverfasser: Ivanovs, Andrejs, Rybtsov, Stanislav, Welch, Lindsey, Anderson, Richard A, Turner, Marc L, Medvinsky, Alexander
Format: Journal Article
Sprache:Englisch
Veröffentlicht: United States 21.11.2011
Schlagworte:
Animals
Aorta - cytology
Aorta - embryology
Cell Proliferation
Embryo, Mammalian - cytology
Embryo, Mammalian - embryology
Flow Cytometry
Gonads - cytology
Gonads - embryology
Hematopoiesis - physiology
Hematopoietic Stem Cells - cytology
Humans
Mesonephros - cytology
Mesonephros - embryology
Mice
Mice, SCID
Regenerative Medicine - methods
ISSN:1540-9538, 1540-9538
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Zusammenfassung:Hematopoietic stem cells (HSCs) emerge during embryogenesis and maintain hematopoiesis in the adult organism. Little is known about the embryonic development of human HSCs. We demonstrate that human HSCs emerge first in the aorta-gonad-mesonephros (AGM) region, specifically in the dorsal aorta, and only later appear in the yolk sac, liver, and placenta. AGM region cells transplanted into immunodeficient mice provide long-term high level multilineage hematopoietic repopulation. Human AGM region HSCs, although present in low numbers, exhibit a very high self-renewal potential. A single HSC derived from the AGM region generates at least 300 daughter HSCs in primary recipients, which disseminate throughout the entire recipient bone marrow and are retransplantable. These findings highlight the vast regenerative potential of the earliest human HSCs and set a new standard for in vitro generation of HSCs from pluripotent stem cells for the purpose of regenerative medicine.
Bibliographie:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
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ISSN:1540-9538
1540-9538
DOI:10.1084/jem.20111688