Stem Cell Reports
Volume 12, Issue 5, 14 May 2019, Pages 1056-1068
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Article
Analysis of the Spatiotemporal Development of Hematopoietic Stem and Progenitor Cells in the Early Human Embryo

https://doi.org/10.1016/j.stemcr.2019.03.003Get rights and content
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Highlights

  • Ex vivo culture efficiently expands CFU-Cs derived from human embryonic tissue

  • Human AGM-derived HSCs can be maintained in explant culture

  • Human HSCs emerge predominantly in the middle section of the dorsal aorta

Summary

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.

Keywords

hematopoietic stem cells
hematopoietic progenitors
human embryo
yolk sac
fetal liver

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