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Origins of Hematopoietic Stem Cells
Author(s) -
Dzierzak Elaine
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a85-d
Subject(s) - dorsal aorta , hemangioblast , biology , haematopoiesis , microbiology and biotechnology , stem cell , yolk sac , endothelium , embryonic stem cell , bone marrow , anatomy , immunology , embryo , genetics , gene
Hematopoietic stem cells (HSC) are the source of adult blood cells. These clinically relevant HSCs are harbored in the bone marrow, umbilical cord blood and fetal liver. At earliest stages of development, hematopoietic cells share a close association with the vasculature. Molecular and cellular studies have provided strong evidence for a common mesodermal precursor for the endothelial and hematopoietic lineages. However, there is little understanding concerning the dynamic and diverse embryonic microenvironments that trigger the fate determination and growth of HSCs. During mouse midgestation, HSCs are harbored intraembryonically in the AGM (aorta‐gonad‐mesonephros) region; the extraembryonic sites include yolk sac and placenta; and the large vessels (vitelline and umbilical arteries) connecting the intra and extraembryonic tissues also contain HSCs. As the first site to autonomously generate HSCs, the AGM has been the focus of our efforts to identify the molecular components and cellular interactions involved in the HSC generation process. Spatial localization studies show that emergent HSCs are localized within the endothelium of the ventral wall of the dorsal aorta and appear to be generated from a temporally restricted subset of endothelial cells, ‘hemogenic endothelium’. Some of the signaling pathways active in this region at the time of HSC generation will be discussed.