New Genes Controlling Neural Stem Cell Differentiation

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哺乳动物皮层中。这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，一些长链非编码rna以及具有高度特异性和瞬时表达模式的全新基因。我们最近的工作提供了迄今为止最全面和定量的神经干细胞从增殖到分化转换过程中的转录组资源，并确定了一系列完全未知的基因，这些基因可能在哺乳动物皮质发生过程中发挥重要作用。当前应用的目的是进行功能实验，以表征一些候选新基因作用的分子机制，为组织形成和体内平衡过程中神经干细胞的调节提供更多的见解。

Transcriptome analysis of somatic stem cells and their progeny is fundamental to identify the molecular mechanisms regulating the transition from proliferation to differentiation. However, analyzing 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 mammalian cortex. Transcriptome sequencing of these three cell types revealed numerous uncharacterized protein-coding genes, several long non-coding RNAs as well as completely new genes with a highly specific and transient expression pattern. Our recent work provides the most comprehensive and quantitative trascriptome resource during the switch of neural stem from proliferation to differentiation to date and identifies a list of completely uncharacterized genes likely playing important roles during mammalian corticogenesis. The purpose of the current application is to perform the functional experiments needed to characterize the molecular mechanisms underlying the action of some of these candidate new genes providing more insight into neural stem cell regulation during tissue formation and homeostasis.