Regulation of microRNA Expression and Abundance during Lymphopoiesis

Although the cellular concentration of miRNAs is critical to their function, how miRNA expression and abundance are regulated during ontogeny is unclear. We used deep-sequencing to characterize the microRNome from most developing lymphocytes, various hematopoietic cell lineages, and representative mouse tissues. Epigenetic and transcriptome profiles were also compiled from selected T and B cell stages by ChIP-Seq and mRNA-Seq respectively. We show that lymphocyte-specific miRNAs are either tightly regulated during development by polycomb group-mediated H3K27me3, or maintained in a semi-activated state prior to full expression. Because of extensive miRNA biogenesis, the cellular concentration of mature miRNAs does not typically reflect transcriptional changes. However, we here uncovered a subset of miRNAs for which abundance is directly regulated by miRNA gene expression. Our data provides the most comprehensive view of the microRNome in the immune system and reveal underlying epigenetic and transcriptional forces that shape miRNA homeostasis. small RNA expression profiles of 27 well defined cell types from the mouse immune system, hematopoietic progenitor cells, embryonic stem cells, as well as 12 tissues. Biological and technical replicates for 3 of the cell types were included. Regulation of MicroRNA Expression and Abundance during Lymphopoiesis Immunity, Volume 32, Issue 6, 25 June 2010, Pages 828-839 doi:10.1016/j.immuni.2010.05.009