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

• DOI: 10.1016/j.stem.2016.06.008
• Publication Date: 2016-07-16T05:28:30Z
• Authors: Edyta E. Wojtowicz; Eric R. Lechman; Karin G. Hermans; Erwin M. Schoof; Erno Wienholds; Ruth Isserlin; Peter A. van Veelen; Mathilde J.C. Bro...; George M.C. Janssen; Aaron Trotman-Grant; Stephanie M. Dobson; Gabriela Krivdova; Jantje Elzinga; James Kennedy; Olga I. Gan; Ankit Sinha; Vladimir Ignatchenko; Thomas Kislinger; Bertien Dethmers-...; Ellen Weersing; Mir Farshid Alemdehy; Hans W.J. de Looper; Gary D. Bader; Martha Ritsema; Stefan J. Erkeland; Leonid V. Bystrykh; John E. Dick; Gerald de Haan
• Keywords: Ectopic expression; Hematopoietic stem cell

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.