Transcriptional Hallmarks of Heterogeneous Neural Stem Cell Niches of the Subventricular Zone
Transcriptional Hallmarks of Heterogeneous Neural Stem Cell Niches of the Subventricular Zone
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DOI：
10.1002/stem.2017
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发表时间：
2015-07-01
期刊：
影响因子：
5.2
通讯作者：
Raineteau, Olivier
中科院分区：
文献类型：
--
作者：
Azim, Kasum;Hurtado-Chong, Anahi;Raineteau, Olivier
在哺乳动物的整个出生后生命中，神经干细胞（NSC）位于侧脑室的室下区（SVZ）。它们产生的神经元和神经胶质谱系的最大多样性发生在出生后早期以区域特异性的方式。为了探究出生后 SVZ 的异质性，我们在不同出生后年龄对其背壁和侧壁进行显微解剖，并分别根据 Hes5-EGFP/Prominin1 和 Ascl1-EGFP 的表达分离 NSC 及其直系后代。全基因组比较转录组分析揭示转录调节因子是维持出生后 SVZ 区域化的主要标志。编码局部富集转录因子（体内功能丧失或异位功能获得）的单基因操作影响 NSC 规范，表明区域化的出生后 SVZ-NSC 的命运可以很容易地改变。这些发现揭示了出生后 SVZ 明显的转录异质性，并为在再生环境中招募区域特异性谱系提供了靶标。干细胞 2015；33：2232-2242
Throughout postnatal life in mammals, neural stem cells (NSCs) are located in the subventricular zone (SVZ) of the lateral ventricles. The greatest diversity of neuronal and glial lineages they generate occurs during early postnatal life in a region-specific manner. In order to probe heterogeneity of the postnatal SVZ, we microdissected its dorsal and lateral walls at different postnatal ages and isolated NSCs and their immediate progeny based on their expression of Hes5-EGFP/Prominin1 and Ascl1-EGFP, respectively. Whole genome comparative transcriptome analysis revealed transcriptional regulators as major hallmarks that sustain postnatal SVZ regionalization. Manipulation of single genes encoding for locally enriched transcription factors (loss-of-function or ectopic gain-of-function in vivo) influenced NSC specification indicating that the fate of regionalized postnatal SVZ-NSCs can be readily modified. These findings reveal the pronounced transcriptional heterogeneity of the postnatal SVZ and provide targets to recruit region-specific lineages in regenerative contexts. Stem Cells 2015;33:2232-2242