| Literature DB >> 27424784 |
Edyta E Wojtowicz1, Eric R Lechman2, Karin G Hermans2, Erwin M Schoof2, Erno Wienholds2, Ruth Isserlin3, Peter A van Veelen4, Mathilde J C Broekhuis1, George M C Janssen4, Aaron Trotman-Grant2, Stephanie M Dobson5, Gabriela Krivdova5, Jantje Elzinga2, James Kennedy2, Olga I Gan2, Ankit Sinha6, Vladimir Ignatchenko6, Thomas Kislinger6, Bertien Dethmers-Ausema1, Ellen Weersing1, Mir Farshid Alemdehy7, Hans W J de Looper7, Gary D Bader3, Martha Ritsema1, Stefan J Erkeland8, Leonid V Bystrykh1, John E Dick9, Gerald de Haan10.
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.Entities:
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Year: 2016 PMID： 27424784 PMCID： PMC5500905 DOI： 10.1016/j.stem.2016.06.008
Source DB: PubMed Journal: Cell Stem Cell ISSN： 1875-9777 Impact factor: 24.633