Expression of the miR-221/222 cluster can safeguards transplanted HSC from loss of lymphoid-myeloid multipotency

Abstract

A microRNA cluster, miR‑221/222, is expressed in quiescent and activated HSC of mice. The expressions of fos and jun, hence AP-1, and a collection of other immediate early genes (IEG), are up-regulated in miR-221/222-deficient HSC. Social stress and HSC transplantation induces comparable up-regulation of IEGs. Stress, as well as miR-221/222-deficiency leads to decreases in the numbers of quiescent HSC and increases in the number of activated hematopoietic (MPP2-4) progenitors, as well as numbers of progenitors of emergency granulopoiesis. Serial transplantations of miR-221/222-deficient HSC generated HSC in the recipient bone marrow, prematurely lose their lymphoid repopulation capacities – normally a sign of aged HSC. Consequently, enforced expression of miR-221/222 should preserve and enhance lymphoid potency of HSC. These results suggest that the expression of miR-221/222 genes themselves and target genes of miR-221/222 in HSC should improve HSC performance in bone marrow niches and their lymphoid development in the transplanted host. Since the miR-221 and -222 genes are also expressed in human HSC, it is likely, that these new targets should be applicable to the improvement of human bone marrow transplantation.