MiR-125a Confers Multi-Lineage Long-Term Repopulating Stem Cell Activity to Murine and Human Hematopoietic Progenitors

ABSTRACT: Umbilical cord blood (CB) is a non-invasive, 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. One feasible option would be to expand HSCs to improve therapeutic outcome, however available protocols and the molecular mechanisms governing the self-renewal of HSC are unclear. Here we show that ectopic expression of a single miRNA, miR-125a, in purified murine and human multipotent progenitors (MPP) 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 which revealed the involvement of the MAP kinase signaling pathway in conferring long-term repopulating capacity to multipotent progenitors in human and mice. Our findings offer the innovative potential to use MPP with enhanced self-renewal activity to augment limited sources of HSC to improve clinical protocols.

INSTRUMENT(S): Orbitrap Fusion ETD

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Blood Cell, Stem Cell, Blood

DISEASE(S): Disease Free

SUBMITTER: Erwin Schoof  

LAB HEAD: John E. Dick

PROVIDER: PXD003931 | Pride | 2017-01-11

REPOSITORIES: Pride