Prospective isolation and molecular characterization of hematopoietic stem cells with durable self-renewal potential

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Abstract

Hematopoietic stem cells (HSCs) are generally defined by their dual properties of pluripotency and extensive self-renewal capacity. However, a lack of experimental clarity as to what constitutes extensive self-renewal capacity coupled with an absence of methods to prospectively isolate long-term repopulating cells with defined self-renewal activities has made it difficult to identify the essential components of the self-renewal machinery and investigate their regulation. We now show that cells capable of repopulating irradiated congenic hosts for 4 months and producing clones of cells that can be serially transplanted are selectively and highly enriched in the CD150+ subset of the EPCR+CD48+CD45+ fraction of mouse fetal liver and adult bone marrow cells. In contrast, cells that repopulate primary hosts for the same period but show more limited self-renewal activity are enriched in the CD150- subset. Comparative transcriptome analyses of these 2 subsets with each other and with HSCs whose self-renewal activity has been rapidly extinguished in vitro revealed 3 new genes (VWF, Rhob, Pld3) whose elevated expression is a consistent and selective feature of the long-term repopulating cells with durable self-renewal capacity. These findings establish the identity of a phenotypically and molecularly distinct class of pluripotent hematopoietic cells with life-long self-renewal capacity. © 2009 by The American Society of Hematology.

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Kent, D. G., Copley, M. R., Benz, C., Wöhrer, S., Dykstra, B. J., Ma, E., … Eaves, C. J. (2009). Prospective isolation and molecular characterization of hematopoietic stem cells with durable self-renewal potential. Blood, 113(25), 6342–6350. https://doi.org/10.1182/blood-2008-12-192054

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