Differential microRNA expression between bone marrow side population cells and hepatocytes in adult mice.

Hematopoietic stem cells (HSCs) can differentiate into many kinds of parenchymal cells populating several organs. Nevertheless, the differentiation mechanism of HSCs toward hepatocytes remains poorly understood. To identify specific microRNAs (miRNAs) contributing to the mechanism, we investigated the differential expression of miRNAs between side population (SP) cells of bone marrow and hepatocytes in adult mice. We used a miRNA microarray followed by stem-loop-mediated reverse transcription real-time PCR to identify 12 SP-specific and 2 hepatocyte-specific miRNAs. Of these, 3 (miR-451, -150 and -223) were strongly expressed (>10-fold relative enrichment) in SP cells. Two of these miRNAs (miR-451 and -223) were strongly associated with the hematic cell lineage but not with progenitor characteristics. Two-thirds (6/9) of the miRNAs that were moderately expressed in SP cells in comparison with hepatocytes were also up-regulated in potential hepatic stem cells (HSCEs). The single miRNA (miRNA-127) that was up-regulated in SP cells compared with lineage-positive bone marrow cells might be an SP marker, since it was markedly down-regulated in HSCEs. These results suggest that SP cells and HSCE share a common profile of miRNA expression and that miRNA-127 may contribute to the maintenance of a quiescent state in SP cells.