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Cell Stem Cell. 2016 Sep 1;19(3):383-96. doi: 10.1016/j.stem.2016.06.008. Epub 2016 Jul 14.

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

Author information

1
Laboratory of Ageing Biology and Stem Cells, European Research Institute for the Biology of Ageing, University Medical Centre Groningen, University of Groningen, Antonius Deusinglaan 1, 9700 AV Groningen, the Netherlands.
2
Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 1L7, Canada.
3
The Donnelly Centre, University of Toronto, Toronto, ON M5S 3E1, Canada.
4
Departments of Immunohematology and Blood Transfusion, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands.
5
Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 1L7, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada.
6
Department of Medical Biophysics, University of Toronto, Toronto, ON M5G 1L7, Canada.
7
Department of Hematology, Erasmus University Medical Center Cancer Institute, Wytemaweg 80, 3015 CN Rotterdam, the Netherlands.
8
Department of Immunology, Erasmus University Medical Center, Wytemaweg 80, 3015CN Rotterdam, the Netherlands.
9
Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 1L7, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada. Electronic address: jdick@uhnres.utoronto.ca.
10
Laboratory of Ageing Biology and Stem Cells, European Research Institute for the Biology of Ageing, University Medical Centre Groningen, University of Groningen, Antonius Deusinglaan 1, 9700 AV Groningen, the Netherlands. Electronic address: g.de.haan@umcg.nl.

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.

PMID:
27424784
PMCID:
PMC5500905
DOI:
10.1016/j.stem.2016.06.008
[Indexed for MEDLINE]
Free PMC Article

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