Ectopic miR-125a Expression Induces Long-Term Repopulating Stem Cell Capacity in Mouse and Human Hematopoietic Progenitors.
Cell Stem Cell
; 19(3): 383-96, 2016 09 01.
Article
in En
| MEDLINE
| ID: mdl-27424784
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Hematopoietic Stem Cells
/
Gene Expression Regulation
/
MicroRNAs
Type of study:
Guideline
/
Prognostic_studies
Limits:
Animals
/
Humans
/
Male
Language:
En
Journal:
Cell Stem Cell
Year:
2016
Document type:
Article
Affiliation country:
Netherlands