Long Non-Coding RNAs and Alternative Splicing Control Cortical Development

体细胞干细胞及其后代的转录组分析是确定从增殖到分化的调节分子机制的基础。然而，分析复杂组织中单个细胞类型的转录组仍然是一个挑战。我们建立了一个RFP/GFP双报告小鼠系来分离增殖的神经干细胞，分化祖细胞和新生神经元，它们作为混合细胞群共存于发育中的大脑中。三种细胞类型的转录组测序揭示了许多未表征的蛋白质编码基因以及具有高度特异性和瞬时表达模式的长链非编码（lnc） rna，并表征了神经源性承诺的特征。在体内操纵这样一种lncRNA可能通过调节选择性剪接强烈影响神经干细胞分化和皮质发生过程中的神经元存活。在这个项目中，我们的目标是剖析所观察到的表型背后的分子和细胞效应，并探索脑形成过程中选择性剪接在神经干细胞动力学中的作用。

Transcriptome analysis of somatic stem cells and their progeny is fundamental to identify the molecular mechanisms regulating the switch from proliferation to differentiation. However, analysing transcriptomes of individual cell types in complex tissues remains a challenge. We generated a RFP/GFP double-reporter mouse line to isolate proliferating neural stem cells, differentiating progenitors and newborn neurons that coexist as intermingled cell populations in the developing brain. Transcriptome sequencing of the three cell types revealed numerous uncharacterized protein-coding genes as well as long non-coding (lnc)RNAs with highly specific and transient expression patterns and characterizing the signature of neurogenic commitment. In vivo manipulation of one such lncRNA strongly influenced neural stem cell differentiation and neuronal survival during corticogenesis likely through a regulation of alternative splicing. With this project we aim to dissect the molecular and cellular effects underlying the observed phenotypes and explore the role of alternative splicing in neural stem cell dynamics during brain formation.