Delineation of mammary transcriptome has identified molecular pathways that regulate self-renewal, lineage commitment and differentiation along the cellular hierarchy. The epigenetic landscape of mammary epithelial subsets has also revealed underlying chromatin modifications responsible for lineage specification. However the expression profile of microRNAs and their influence on the mammary transcriptome is not fully known. We therefore carried out genome-wide microRNA expression analysis of four distinct murine and human mammary epithelial subpopulations: stem cell-enriched, luminal progenitor, mature luminal and stromal cells.
The mouse mammary epithelial subpopulations exhibit distinct microRNA and target mRNA signatures, which are substantially conserved with their human counterparts and are likely to govern cell-fate decisions and differentiation. The comparison of miR signatures between mouse mammary epithelium and different mouse models of mammary tumorigenesis identified signalling pathways that are targeted by miRs during mammary tumorigenesis. Interestingly, interrogation of the genome-wide histone methylation profiles with microRNA expression data showed a tight correlation between microRNA expression and specific epigenetic modifications.