Extensive hematopoietic stem cell generation in the AGM region via maturation of VE-cadherin+CD45+ pre-definitive HSCs.
Elucidating the mechanisms underlying hematopoietic stem cell (HSC) specification and expansion in the embryo has been hampered by the lack of analytical cell culture systems that recapitulate in vivo development. Here, we describe an ex vivo model that facilitates a rapid and robust emergence of multipotent long-term repopulating HSCs in the embryonic AGM region. Because this method includes a cell dissociation step prior to reconstruction of a three-dimensional functional tissue and preserves both stromal and hematopoietic elements, it allowed us to identify the direct ancestry of the rapidly expanding HSC pool. We demonstrate that extensive generation of definitive HSCs in the AGM occurs predominantly through the acquisition of stem characteristics by the VE-cadherin+CD45+ population.
Taoudi
Samir
S
MRC Centre for Regenerative Medicine, Institute for Stem Cell Research, University of Edinburgh, Edinburgh EH9 3JQ, UK.
Gonneau
Christèle
C
Moore
Kate
K
Sheridan
Julie M
JM
Blackburn
C Clare
CC
Taylor
Erin
E
Medvinsky
Alexander
A
D000818:Animals; D015703:Antigens, CD / Q000502:physiology*; D015820:Cadherins / Q000502:physiology*; D018929:Cell Culture Techniques / Q000379:methods; D002460:Cell Line; D003114:Colony-Forming Units Assay; D005434:Flow Cytometry; D005819:Genetic Markers; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000502:physiology*; D006801:Humans; D017493:Leukocyte Common Antigens / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000099152:Cadherin 5
D015703:Antigens, CD; D015820:Cadherins; D005819:Genetic Markers; D017493:Leukocyte Common Antigens; D000099152:Cadherin 5