Wojtowicz EE, Lechman ER, Hermans KG, Schoof EM, Wienholds E, Isserlin R, van Veelen PA, Broekhuis MJ, Janssen GM, Trotman-Grant A, Dobson SM, Krivdova G, Elzinga J, Kennedy J, Gan OI, Sinha A, Ignatchenko V, Kislinger T, Dethmers-Ausema B, Weersing E, Alemdehy MF, de Looper HW, Bader GD, Ritsema M, Erkeland SJ, Bystrykh LV, Dick JE, de Haan G

Cell Stem Cell 2016 Jul;

PMID: 27424784

Abstract

Umbilical cord blood (CB) is a convenient and broadly used source of hematopoietic stem cells (HSCs) for allogeneic stem cell transplantation. However, limiting numbers of HSCs remain a major constraint for its clinical application. Although one feasible option would be to expand HSCs to improve therapeutic outcome, available protocols and the molecular mechanisms governing the self-renewal of HSCs are unclear. Here, we show that ectopic expression of a single microRNA (miRNA), miR-125a, in purified murine and human multipotent progenitors (MPPs) resulted in increased self-renewal and robust long-term multi-lineage repopulation in transplanted recipient mice. Using quantitative proteomics and western blot analysis, we identified a restricted set of miR-125a targets involved in conferring long-term repopulating capacity to MPPs in humans and mice. Our findings offer the innovative potential to use MPPs with enhanced self-renewal activity to augment limited sources of HSCs to improve clinical protocols.

Ectopic miR-125a Expression Induces Long-Term Repopulating Stem Cell Capacity in Mouse and Human Hematopoietic Progenitors
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