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

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 the...

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Veröffentlicht in:	Cell stem cell Jg. 19; H. 3; S. 383
Hauptverfasser:	Wojtowicz, Edyta E, Lechman, Eric R, Hermans, Karin G, Schoof, Erwin M, Wienholds, Erno, Isserlin, Ruth, van Veelen, Peter A, Broekhuis, Mathilde J C, Janssen, George M C, Trotman-Grant, Aaron, Dobson, Stephanie M, Krivdova, Gabriela, Elzinga, Jantje, Kennedy, James, Gan, Olga I, Sinha, Ankit, Ignatchenko, Vladimir, Kislinger, Thomas, Dethmers-Ausema, Bertien, Weersing, Ellen, Alemdehy, Mir Farshid, de Looper, Hans W J, Bader, Gary D, Ritsema, Martha, Erkeland, Stefan J, Bystrykh, Leonid V, Dick, John E, de Haan, Gerald
Format:	Journal Article
Sprache:	Englisch
Veröffentlicht:	United States 01.09.2016
Schlagworte:	ADP-ribosyl Cyclase 1 - metabolism Animals Antigens, CD34 - metabolism Cell Proliferation Cell Self Renewal - genetics Gene Expression Regulation Gene Regulatory Networks Hematopoietic Stem Cell Transplantation Hematopoietic Stem Cells - cytology Hematopoietic Stem Cells - metabolism Humans Isotope Labeling Male Mice, Inbred C57BL MicroRNAs - genetics MicroRNAs - metabolism Models, Biological Multipotent Stem Cells - cytology Multipotent Stem Cells - metabolism Multipotent Stem Cells - transplantation Reproducibility of Results Time Factors
ISSN:	1875-9777, 1875-9777
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Zusammenfassung:	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.
Bibliographie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1875-9777 1875-9777
DOI:	10.1016/j.stem.2016.06.008