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Analysis of the Spatiotemporal Development of Hematopoietic Stem and Progenitor Cells in the Early Human Embryo.

TitleAnalysis of the Spatiotemporal Development of Hematopoietic Stem and Progenitor Cells in the Early Human Embryo.
Publication TypeJournal Article
Year of Publication2019
AuthorsEasterbrook J, Rybtsov S, Gordon-Keylock S, Ivanovs A, Taoudi S, Anderson RA, Medvinsky AL
JournalStem Cell Reports
Volume12
Issue5
Pagination1056-1068
Date Published2019 May 14
ISSN2213-6711
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.

DOI10.1016/j.stemcr.2019.03.003
Alternate JournalStem Cell Reports
PubMed ID30956115
PubMed Central IDPMC6525107
Grant List / / Wellcome Trust / United Kingdom
Publication institute
CRM