Browsing by Author "Medvinsky, Alexander"

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    Analysis of the Spatiotemporal Development of Hematopoietic Stem and Progenitor Cells in the Early Human Embryo
    (2019-05-14) Easterbrook, Jennifer; Rybtsov, Stanislav; Gordon-Keylock, Sabrina; Ivanovs, Andrejs; Taoudi, Samir; Anderson, Richard A.; Medvinsky, Alexander
    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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    Human haematopoietic stem cell development : From the embryo to the dish
    (2017) Ivanovs, Andrejs; Rybtsov, Stanislav; Ng, Elizabeth S.; Stanley, Edouard G.; Elefanty, Andrew G.; Medvinsky, Alexander
    Haematopoietic stem cells (HSCs) emerge during embryogenesis and give rise to the adult haematopoietic system. Understanding how early haematopoietic development occurs is of fundamental importance for basic biology and medical sciences, but our knowledge is still limited compared with what we know of adult HSCs and their microenvironment. This is particularly true for human haematopoiesis, and is reflected in our current inability to recapitulate the development of HSCs from pluripotent stem cells in vitro. In this Review, we discuss what is known of human haematopoietic development: the anatomical sites at which it occurs, the different temporal waves of haematopoiesis, the emergence of the first HSCs and the signalling landscape of the haematopoietic niche. We also discuss the extent to which in vitro differentiation of human pluripotent stem cells recapitulates bona fide human developmental haematopoiesis, and outline some future directions in the field.