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    Activation of the Receptor Tyrosine Kinase, RET, improves long-term Hematopoietic Stem Cell outgrowth and potency

    Grey, W. and Chauhan, R. and Piganeau, M. and Huerga, E. and Garcia-Albornoz, M. and McDonald, Neil and Bonnet, D. (2020) Activation of the Receptor Tyrosine Kinase, RET, improves long-term Hematopoietic Stem Cell outgrowth and potency. Blood , ISSN 0006-4971. (In Press)

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    Abstract

    Expansion of Human Hematopoietic Stem Cells (HSCs) is a rapidly advancing field showing great promise for clinical applications. Recent evidence has implicated the nervous system and glial family ligands (GFLs) as potential drivers of hematopoietic survival and self-renewal in the bone marrow niche, but how to apply this to HSC maintenance and expansion is yet to be explored. We demonstrate a role for the GFL receptor, RET, at the cell surface of HSCs, in mediating sustained cellular growth, resistance to stress and improved cell survival throughout in vitro expansion. HSCs treated with the key RET ligand/co-receptor complex, GDNF/GFRa1, show improved progenitor function at primary transplantation and improved long-term HSC function at secondary transplantation. Finally, we demonstrate that RET drives a multi-faceted intracellular signalling pathway, including key signalling intermediates AKT, ERK1/2, NFkB and p53, responsible for a wide range of cellular and genetic responses which improve cell growth and survival under culture conditions.

    Metadata

    Item Type: Article
    School: School of Science > Biological Sciences
    Research Centres and Institutes: Structural Molecular Biology, Institute of (ISMB)
    Depositing User: Neil McDonald
    Date Deposited: 16 Jul 2020 12:29
    Last Modified: 17 Jul 2020 22:17
    URI: https://eprints.bbk.ac.uk/id/eprint/32542

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