Analysis of the Spatiotemporal Development of Hematopoietic Stem and Progenitor Cells in the Early Human Embryo
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2019-05-14
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Abstract
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.
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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
Keywords
fetal liver, hematopoietic progenitors, hematopoietic stem cells, human embryo, yolk sac, 3.1 Basic medicine, 3.2 Clinical medicine, 1.6 Biological sciences, 3.3 Health sciences, 1.1. Scientific article indexed in Web of Science and/or Scopus database, Biochemistry, Genetics, Developmental Biology, Cell Biology, SDG 3 - Good Health and Well-being
Citation
Easterbrook, J, Rybtsov, S, Gordon-Keylock, S, Ivanovs, A, Taoudi, S, Anderson, R A & Medvinsky, A 2019, 'Analysis of the Spatiotemporal Development of Hematopoietic Stem and Progenitor Cells in the Early Human Embryo', Stem Cell Reports, vol. 12, no. 5, pp. 1056-1068. https://doi.org/10.1016/j.stemcr.2019.03.003