Journal
CELL STEM CELL
Volume 19, Issue 3, Pages 383-396Publisher
CELL PRESS
DOI: 10.1016/j.stem.2016.06.008
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Funding
- Netherlands Organization for Scientific Research
- Canadian Institutes for Health Research (CIHR) fellowship
- EuroCSCTraining Eurocancer Stemcell Training Network ITN-FP7-Marie Curie Action [264361]
- Netherlands Institute for Regenerative Medicine
- European Commission [GA-2013-609409]
- Marie Curie Actions
- CIHR
- Canadian Cancer Society Research Institute
- Terry Fox Foundation
- Genome Canada through the Ontario Genomics Institute
- Ontario Institute for Cancer Research
- Canada Research Chair
- Princess Margaret Hospital Foundation
- Ontario Ministry of Health and Long Term Care (OMOHLTC)
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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 selfrenewal 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.
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