MicroRNA programs in normal and aberrant stem and progenitor cells. Mus musculus

Emerging evidence suggests that microRNAs (miRNAs), an abundant class of ~22-nt small regulatory RNAs, play key roles in controlling the post-transcriptional genetic programs in stem and progenitor cells. Here we systematically examined miRNA expression profiles in various adult tissue-specific stem cells and their differentiated counterparts. These analyses revealed miRNA programs that are common or unique to blood, muscle, and neural stem cell populations and miRNA signatures that mark the transitions from self-renewing and quiescent stem cells to proliferative and differentiating progenitor cells. Moreover, we found a stem/progenitor transition miRNA (SPT-miRNA) signature that predicts the effects of genetic perturbations, such as loss of PTEN and the Rb family, AML-ETO expression, and MLL-AF10 transformation, on self-renewal, proliferation, and/or differentiation potentials of mutant stem/progenitor cells. More importantly, some SPT-miRNAs can control rate of self-renewal in embryonic stem cells and the reconstitution potential of hematopoietic stem cells (HSCs). Finally, we found that some SPT-miRNAs may coordinately regulate genes that are known to play roles in controlling HSC self-renewal, such as Hoxb6 and Hoxa4. Together, these analyses revealed the miRNA programs that control key processes in normal and aberrant stem and progenitor cells, setting the foundations for dissecting post-transcriptional regulatory networks in stem cells. Overall design: We used a multiplex protocol to amplify miRNAs from 20-1000 sorted stem and/or progenitor cells and then analyzed the expression of 425 mature miRNAs using TaqMan miRNA quantitative PCR analyses