| Abstract: |
MicroRNAs profoundly impact hematopoietic cells by regulating progenitor cell-fate decisions, as well as mature immune effector function. However to date, microRNAs that regulate hematopoietic stem cell (HSC) function have been less well characterized. Here we show that microRNA-125b (miR-125b) is highly expressed in HSCs and its expression decreases in committed progenitors. Overexpression of miR-125b in mouse HSC enhances their function, demonstrated through serial transplantation of highly purified HSC, and enriches for the previously described Slamf1 loCD34 - lymphoidbalanced and the Slamf1 negCD34 - lymphoid-biased cell subsets within the multipotent HSC (CD34-KLS) fraction. Mature peripheral blood cells derived from the miR-125b-overexpressing HSC are skewed toward the lymphoid lineage. Consistent with this observation, miR-125b overexpression significantly increases the number of early B-progenitor cells within the spleen and induces the expansion and enrichment of the lymphoid-balanced and lymphoidbiased HSC subset via an antiapoptotic mechanism, reducing the mRNA expression levels of two proapoptotic targets, Bmf and KLF13. The antiapoptotic effect of miR-125b is more pronounced in the lymphoid-biased HSC subset because of their intrinsic higher baseline levels of apoptosis. These effects of miR-125b are associated with the development of lymphoproliferative disease, marked by expansion of CD8 + T lymphocytes. Taken together, these data reveal that miR-125b regulates HSC survival and can promote lymphoid-fate decisions at the level of the HSC by preferentially expanding lymphoid-balanced and lymphoid-biased HSC. |
| Notes: |
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- Proc. Natl. Acad. Sci. U. S. A.
- "Cited By (since 1996): 23 Export Date: 13 July 2012 Source: Scopus CODEN: PNASA PubMed ID: 21118986 Language of Original Document: English Chemicals/CAS: Antigens, CD; Antigens, CD34; CD150 antigen, 169535-43-7; MIRN125 microRNA, human; MicroRNAs; Mirn125 microRNA, mouse; Receptors, Cell Surface"
- "Source: Scopus"
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