MiR-125a enhances self-renewal, lifespan, and migration of murine hematopoietic stem and progenitor cell clones.

Edyta Wójtowicz, M.J.C. Broekhuis, Ellen Weersing, Alexander Dinitzen, Evgenia Verovskaya, Bertien Ausema, Martha Ritsema, Erik Zwart, Gerald de Haan, Leonid Bystrykh

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    Abstract

    Expansion of hematopoietic stem cells (HSCs) is a 'holy grail' of regenerative medicine, as successful stem cell transplantations depend on the number and quality of infused HSCs. Although many attempts have been pursued to either chemically or genetically increase HSC numbers, neither clonal analysis of these expanded cells nor their ability to support mature blood lineages has been demonstrated. Here we show that miR-125a, at the single cell level, can expand murine long-term repopulating HSCs. In addition, miR-125a increases clone longevity, clone size and clonal contribution to hematopoiesis. Unexpectedly, we found that miR-125a expanded HSCs clones were highly homogenously distributed across multiple anatomical sites. Interestingly, these miR-125a overexpressing cells had enhanced mobility and were more frequently detected in the spleen. Our study reveals a novel, cell-intrinsically controlled mechanism by which HSC migration is regulated.
    Original languageEnglish
    Article number4785
    Number of pages13
    JournalScientific Reports
    Volume9
    DOIs
    Publication statusPublished - 2019

    Keywords

    • EXPANSION
    • CAPACITY
    • MOUSE
    • MOBILIZATION

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