Slowly dividing neural progenitors are an embryonic origin of adult neural stem cells
Slowly dividing neural progenitors are an embryonic origin of adult neural stem cells
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DOI：
10.1038/nn.3989
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发表时间：
2015-05-01
影响因子：
25
通讯作者：
Gotoh, Yukiko
中科院分区：
文献类型：
--
作者：
Furutachi, Shohei;Miya, Hiroaki;Gotoh, Yukiko
成体神经干细胞（NSCs）在发育过程中建立的机制尚不清楚。在这项研究中，通过检查组蛋白2B（H2 B）-GFP融合蛋白的保留来分析细胞周期进程，结果显示，在小鼠胚胎神经祖细胞（NPC）的一个子集中，细胞周期在胚胎日（E）13.5和E15.5之间减慢，而其他胚胎NPC继续快速分裂。通过允许在E9.5表达的H2 B-GFP在分裂细胞中变得稀释直到年轻成人阶段，我们确定年轻成人室管膜下区（SEZ）中的大多数NSC起源于这些缓慢分裂的胚胎NPCs。细胞周期蛋白依赖性激酶抑制剂p57在该胚胎亚群中高度表达，并且p57的缺失损害成体NSC的出现。我们的研究结果表明，相当大一部分的成人经济特区神经干细胞是来自一个缓慢分裂的亚群的胚胎NPC，并确定p57作为一个关键因素，在产生这种胚胎起源的成人经济特区神经干细胞。
The mechanism by which adult neural stem cells (NSCs) are established during development is unclear. In this study, analysis of cell cycle progression by examining retention of a histone 2B (H2B)-GFP fusion protein revealed that, in a subset of mouse embryonic neural progenitor cells (NPCs), the cell cycle slows between embryonic day (E) 13.5 and E15.5 while other embryonic NPCs continue to divide rapidly. By allowing H2B-GFP expressed at E9.5 to become diluted in dividing cells until the young adult stage, we determined that a majority of NSCs in the young adult subependymal zone (SEZ) originated from these slowly dividing embryonic NPCs. The cyclin-dependent kinase inhibitor p57 is highly expressed in this embryonic subpopulation, and the deletion of p57 impairs the emergence of adult NSCs. Our results suggest that a substantial fraction of adult SEZ NSCs is derived from a slowly dividing subpopulation of embryonic NPCs and identify p57 as a key factor in generating this embryonic origin of adult SEZ NSCs.