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尽管microRNA（miRNA）的细胞浓度对其功能至关重要，但在个体发育过程中miRNA的表达与丰度是如何被调控的，目前仍不明确。 我们采用深度测序技术，对绝大多数发育中的淋巴细胞、各类造血细胞谱系以及代表性小鼠组织的microRNome（小RNA组）进行了表征。此外，我们还分别通过染色质免疫共沉淀测序（ChIP-Seq）与mRNA测序（mRNA-Seq），针对选定的T、B细胞阶段获取了表观基因组与转录组谱数据。 我们的研究显示，淋巴细胞特异性miRNA要么在发育过程中受多梳蛋白家族介导的H3K27me3修饰进行严格调控，要么在完全表达前维持半激活状态。 由于miRNA的生物发生过程较为复杂，成熟miRNA的细胞浓度通常无法反映转录水平的变化。但我们在本研究中发现了一类miRNA，其丰度直接由miRNA基因的转录表达进行调控。 本数据集提供了目前免疫系统中最为全面的microRNome视图，并揭示了塑造miRNA稳态的潜在表观遗传与转录调控机制。 本数据集包含小鼠免疫系统、造血祖细胞、胚胎干细胞的27种明确定义的细胞类型，以及12种组织的小RNA表达谱。其中3种细胞类型设置了生物学重复与技术重复样本。 本研究文章标题为《淋巴细胞生成过程中miRNA的表达与丰度调控》，刊载于《免疫（Immunity）》2010年6月25日第32卷第6期，页码范围为828-839，DOI:10.1016/j.immuni.2010.05.009