Single-cell transcriptome analyses reveal signals to activate dormant neural stem cells.
Single-cell transcriptome analyses reveal signals to activate dormant neural stem cells.
复制标题
单细胞转录组分析揭示激活休眠神经干细胞的信号
DOI：
10.1016/j.cell.2015.04.001
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发表时间：
2015-05-21
期刊：
影响因子：
64.5
通讯作者：
Li S
中科院分区：
文献类型：
--
作者：
Luo Y;Coskun V;Liang A;Yu J;Cheng L;Ge W;Shi Z;Zhang K;Li C;Cui Y;Lin H;Luo D;Wang J;Lin C;Dai Z;Zhu H;Zhang J;Liu J;Liu H;deVellis J;Horvath S;Sun YE;Li S
组织特异性干细胞的稀缺性及其周围环境的复杂性使得这些细胞的分子表征特别具有挑战性。通过单细胞转录组和加权基因共表达网络分析（WGCNA），我们揭示了成年小鼠前脑神经发生区中CD 133 +/GFAP−室管膜（E）细胞的分子特性。令人惊讶的是，室管膜CD 133 +/GFAP−静止细胞特有的基因网络的突出枢纽基因富含免疫应答基因，以及编码血管生成因子受体的基因。管理血管内皮生长因子（VEGF）激活的CD 133+室管膜神经干细胞（NSC），内衬不仅侧，但也第四脑室，并与碱性成纤维细胞生长因子（bFGF），引起随后的神经谱系分化和迁移。这项研究揭示了在中枢神经系统的心室表面存在休眠的室管膜神经干细胞，以及在损伤后激活它们的丰富信号。
The scarcity of tissue-specific stem cells and the complexity of their surrounding environment have made molecular characterization of these cells particularly challenging. Through single-cell transcriptome and weighted gene co-expression network analysis (WGCNA), we uncovered molecular properties of CD133+/GFAP− ependymal (E) cells in the adult mouse forebrain neurogenic zone. Surprisingly, prominent hub genes of the gene network unique to ependymal CD133+/GFAP− quiescent cells were enriched for immune-responsive genes, as well as genes encoding receptors for angiogenic factors. Administration of vascular endothelial growth factor (VEGF) activated CD133+ ependymal neural stem cells (NSCs), lining not only the lateral but also the fourth ventricles and, together with basic fibroblast growth factor (bFGF), elicited subsequent neural lineage differentiation and migration. This study revealed the existence of dormant ependymal NSCs throughout the ventricular surface of the CNS, as well as signals abundant after injury for their activation.