TY - JOUR
T1 - Analysis of the Spatiotemporal Development of Hematopoietic Stem and Progenitor Cells in the Early Human Embryo
AU - Easterbrook, Jennifer
AU - Rybtsov, Stanislav
AU - Gordon-Keylock, Sabrina
AU - Ivanovs, Andrejs
AU - Taoudi, Samir
AU - Anderson, Richard A.
AU - Medvinsky, Alexander
N1 - Funding Information:
We thank the patients for donating tissue and A. Saunderson, J. Creiger, and N. Forson for gaining consent from patients and collecting specimens. We thank J. Verth, C. Manson, and their staff for animal maintenance. This work was supported by the Wellcome Trust (grant 100468/Z/12/Z , J.E.) and the MRC (grant G0901577 , A.M.).
Publisher Copyright:
© 2019
PY - 2019/5/14
Y1 - 2019/5/14
N2 - Definitive hematopoietic stem cells (HSCs)first emerge in the aorta-gonad-mesonephros (AGM)region in both mice and humans. An ex vivo culture approach has enabled recapitulation and analysis of murine HSC development. Knowledge of early human HSC development is hampered by scarcity of tissue: analysis of both CFU-C and HSC development in the human embryo is limited. Here, we characterized the spatial distribution and temporal kinetics of CFU-C development within early human embryonic tissues. We then sought to adapt the murine ex vivo culture system to recapitulate human HSC development. We show robust expansion of CFU-Cs and maintenance, but no significant expansion, of human HSCs in culture. Furthermore, we demonstrate that HSCs emerge predominantly in the middle section of the dorsal aorta in our culture system. We conclude that there are important differences between early mouse and human hematopoiesis, which currently hinder the quest to recapitulate human HSC development ex vivo.
AB - Definitive hematopoietic stem cells (HSCs)first emerge in the aorta-gonad-mesonephros (AGM)region in both mice and humans. An ex vivo culture approach has enabled recapitulation and analysis of murine HSC development. Knowledge of early human HSC development is hampered by scarcity of tissue: analysis of both CFU-C and HSC development in the human embryo is limited. Here, we characterized the spatial distribution and temporal kinetics of CFU-C development within early human embryonic tissues. We then sought to adapt the murine ex vivo culture system to recapitulate human HSC development. We show robust expansion of CFU-Cs and maintenance, but no significant expansion, of human HSCs in culture. Furthermore, we demonstrate that HSCs emerge predominantly in the middle section of the dorsal aorta in our culture system. We conclude that there are important differences between early mouse and human hematopoiesis, which currently hinder the quest to recapitulate human HSC development ex vivo.
KW - fetal liver
KW - hematopoietic progenitors
KW - hematopoietic stem cells
KW - human embryo
KW - yolk sac
UR - http://www.scopus.com/inward/record.url?scp=85065158624&partnerID=8YFLogxK
U2 - 10.1016/j.stemcr.2019.03.003
DO - 10.1016/j.stemcr.2019.03.003
M3 - Article
C2 - 30956115
AN - SCOPUS:85065158624
SN - 2213-6711
VL - 12
SP - 1056
EP - 1068
JO - Stem Cell Reports
JF - Stem Cell Reports
IS - 5
ER -
