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.

doi.org/10.1016/j.stem.2016.06.008, hdl.handle.net/1765/97402
Cell Stem Cell
Department of Hematology

Wojtowicz, E.E. (Edyta E.), Lechman, E.R. (Eric R.), Hermans, K., Schoof, E.M. (Erwin M.), Wienholds, E. (Erno), Isserlin, R. (Ruth), … de Haan, G. (2016). Ectopic miR-125a Expression Induces Long-Term Repopulating Stem Cell Capacity in Mouse and Human Hematopoietic Progenitors. Cell Stem Cell, 19(3), 383–396. doi:10.1016/j.stem.2016.06.008