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持续表达 VCAM1 在放射状胶质细胞中是胚胎起源的神经干细胞的出生后所需。

Persistent Expression of VCAM1 in Radial Glial Cells Is Required for the Embryonic Origin of Postnatal Neural Stem Cells.

机构信息

Center for Stem Cell Biology and Regenerative Medicine, School of Medicine, IDG/McGovern Institute for Brain Research, Tsinghua University, Beijing, China; Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing, China; Department of Neurobiology, Beijing Institute for Brain Disorders, Capital Medical University, Beijing, China.

Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing, China.

出版信息

Neuron. 2017 Jul 19;95(2):309-325.e6. doi: 10.1016/j.neuron.2017.06.047.

Abstract

During development, neural stem cells (NSCs) undergo transitions from neuroepithelial cells to radial glial cells (RGCs), and later, a subpopulation of slowly dividing RGCs gives rise to the quiescent adult NSCs that populate the ventricular-subventricular zone (V-SVZ). Here we show that VCAM1, a transmembrane protein previously found in quiescent adult NSCs, is expressed by a subpopulation of embryonic RGCs, in a temporal and region-specific manner. Loss of VCAM1 reduced the number of active embryonic RGCs by stimulating their premature neuronal differentiation while preventing quiescence in the slowly dividing RGCs. This in turn diminished the embryonic origin of postnatal NSCs, resulting in loss of adult NSCs and defective V-SVZ regeneration. VCAM1 affects the NSC fate by signaling through its intracellular domain to regulate β-catenin signaling in a context-dependent manner. Our findings provide new insight on how stem cells in the embryo are preserved to meet the need for growth and regeneration.

摘要

在发育过程中,神经干细胞(NSCs)经历从神经上皮细胞到放射状胶质细胞(RGCs)的转变,随后,一小部分缓慢分裂的 RGCs 产生静息的成年 NSCs,这些细胞存在于脑室下区(V-SVZ)中。在这里,我们发现 VCAM1 是一种先前在静息成年 NSCs 中发现的跨膜蛋白,它以时间和区域特异性的方式在胚胎 RGCs 的亚群中表达。VCAM1 的缺失通过刺激其过早的神经元分化,而阻止缓慢分裂的 RGC 静止,从而减少了活跃的胚胎 RGC 数量。这反过来又减少了出生后 NSCs 的胚胎起源,导致成年 NSCs 的丧失和 V-SVZ 再生的缺陷。VCAM1 通过其细胞内结构域进行信号转导,以依赖于上下文的方式调节β-连环蛋白信号,从而影响 NSC 的命运。我们的发现提供了新的见解,即胚胎中的干细胞是如何被保存下来以满足生长和再生的需要的。

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