Persistent Expression of VCAM1 in Radial Glial Cells Is Required for the Embryonic Origin of Postnatal Neural Stem Cells
Persistent Expression of VCAM1 in Radial Glial Cells Is Required for the Embryonic Origin of Postnatal Neural Stem Cells
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VCAM1 在放射状胶质细胞中的持续表达是出生后神经干细胞胚胎起源所必需的
DOI：
10.1016/j.neuron.2017.06.047
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发表时间：
2017-07-19
期刊：
影响因子：
16.2
通讯作者：
Shen, Qin
中科院分区：
文献类型：
--
作者：
Hu, Xiao-Ling;Chen, Guo;Shen, Qin
在发育过程中，神经干细胞（NSC）经历从神经上皮细胞到放射状胶质细胞（RGCs）的转变，随后，缓慢分裂的RGCs亚群产生静止的成体NSC，其填充脑室-脑室下区（V-SVZ）。在这里，我们表明，VCAM 1，一个跨膜蛋白以前发现在静止的成年神经干细胞，表达的胚胎RGCs的亚群，在时间和区域特异性的方式。VCAM 1的缺失通过刺激其过早的神经元分化而减少了活跃的胚胎RGC的数量，同时防止缓慢分裂的RGC中的静止。这反过来又减少了出生后神经干细胞的胚胎起源，导致成年神经干细胞的损失和缺陷的V-SVZ再生。VCAM 1通过其胞内结构域的信号传导以环境依赖性方式调节β-连环蛋白信号传导来影响NSC命运。我们的发现为胚胎中的干细胞如何被保存以满足生长和再生的需要提供了新的见解。
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 beta-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.