microRNA profiling of mouse cortical progenitors and neurons reveals miR-486-5p as a regulator of neurogenesis

MicroRNAs (miRNAs) are short (~22 nt) single-stranded non-coding RNAs that regulate gene expression at the post-transcriptional level. Over the past years, many studies have extensively characterized the involvement of miRNA-mediated regulation in neurogenesis and brain development. However, a comprehensive catalog of cortical miRNAs cell-specifically expressed in progenitor types of the developing mammalian cortex is still missing. Overcoming this limitation, here we exploited a double reporter mouse line previously validated by our group to allow the identification of the transcriptional signature to neurogenic commitment and provide the field with the complete atlas of miRNAs expression in proliferating neural stem cells, neurogenic progenitors and newborn neurons during corticogenesis. By extending the currently known list of miRNAs expressed in the mouse brain by over two fold, our study highlights the power of cell type-specific analyses for the detection of transcripts that would otherwise be diluted out when studying bulk tissues. We further exploited our data by predicting putative novel miRNAs and validated the power of our approach by providing novel evidence for the involvement of miR-486 as a novel player in brain development. micro RNA profiles in different cell population (proliferating and differentiating progenitors and newborn neurons) of E14.5 developing mouse cortex. Profiles were obtained by deep-sequencing after small RNA enrichment, using Illumina HiSeq 2500微小RNA（MicroRNAs，miRNAs）是一类长度约为22 nt的单链非编码RNA，可在转录后水平调控基因表达。近年来，诸多研究已全面阐明了miRNA介导的调控过程在神经发生与脑发育中的参与作用。然而，目前仍缺乏针对发育中的哺乳动物大脑皮层中各祖细胞类型特异性表达的皮层miRNA的完整目录。为克服这一局限，本研究利用本团队此前已验证的双报告小鼠品系，实现了对神经发生承诺相关转录特征的精准识别，并为该领域提供了皮层发生过程中增殖性神经干细胞、神经发生祖细胞以及新生神经元内miRNA表达的完整图谱。本研究将已知的小鼠脑内表达的miRNA列表扩充了两倍以上，凸显了细胞类型特异性分析的优势——此类分析可检测到在整块组织研究中会被稀释掩盖的转录本。我们进一步利用所获数据预测了潜在的新型miRNA，并通过验证miR-486作为脑发育新调控因子的全新证据，证实了本研究方法的有效性。本数据集包含E14.5发育小鼠大脑皮层不同细胞群体（增殖性与分化性祖细胞、新生神经元）的microRNA表达谱。该表达谱通过小RNA富集后，采用Illumina HiSeq 2500平台进行深度测序获得。