Brain Research Institute, University of Zurich/ETH Zurich, Zurich, Switzerland.
Inserm U846, Stem Cell and Brain Research Institute, Université de Lyon, Université Lyon 1, Bron, France.
Stem Cells. 2015 Jul;33(7):2232-42. doi: 10.1002/stem.2017. Epub 2015 Apr 23.
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.
在哺乳动物的整个出生后生命过程中，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，具有区域特异性。为了探究出生后 SVZ 的异质性，我们在不同的出生后年龄从小鼠 SVZ 的背侧和外侧壁分离出 NSCs 及其直接祖细胞，基于 Hes5-EGFP/Prominin1 和 Ascl1-EGFP 的表达分别对其进行分离。全基因组比较转录组分析显示转录调节因子是维持出生后 SVZ 区域化的主要特征。操纵单个基因编码的局部富集转录因子（体内功能丧失或异位获得功能）影响 NSC 特化，表明区域化的出生后 SVZ-NSC 的命运可以很容易地被修饰。这些发现揭示了出生后 SVZ 的明显转录异质性，并提供了在再生环境中募集区域特异性谱系的靶点。干细胞 2015；33:2232-2242。
