Title | Analysis of the Spatiotemporal Development of Hematopoietic Stem and Progenitor Cells in the Early Human Embryo. |
Publication Type | Journal Article |
Year of Publication | 2019 |
Authors | Easterbrook J, Rybtsov S, Gordon-Keylock S, Ivanovs A, Taoudi S, Anderson RA, Medvinsky AL |
Journal | Stem Cell Reports |
Volume | 12 |
Issue | 5 |
Pagination | 1056-1068 |
Date Published | 2019 May 14 |
ISSN | 2213-6711 |
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. |
DOI | 10.1016/j.stemcr.2019.03.003 |
Alternate Journal | Stem Cell Reports |
PubMed ID | 30956115 |
PubMed Central ID | PMC6525107 |
Grant List | / / Wellcome Trust / United Kingdom |