SETD4 cells contribute to brain development and maintain adult stem cell reservoir for neurogenesis.
SETD4 cells contribute to brain development and maintain adult stem cell reservoir for neurogenesis.
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SETD4 细胞有助于大脑发育并维持神经发生的成体干细胞库
DOI：
10.1016/j.stemcr.2022.07.017
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发表时间：
2022-09-13
影响因子：
5.9
通讯作者：
Yang, Wei-Jun
中科院分区：
文献类型：
--
作者：
Cai, Sun-Li;Yang, Yao-Shun;Ding, Yan-Fu;Yang, Shu-Hua;Jia, Xi-Zheng;Gu, Yun-Wen;Wood, Chris;Huang, Xue-Ting;Yang, Jin-Shu;Yang, Wei-Jun
细胞静止有助于维持神经干细胞(NSCs)及其随后的再生功能，以应对脑损伤和衰老。然而，神经干细胞从胚胎到成年期处于静止状态的规范和维持在很大程度上仍然不清楚。在这里，使用SET结构域包含蛋白4(SETD4)，一种细胞静止的表观遗传决定因素，我们在成年小鼠脑室下区标记了一个小而长的NSC群体处于深度静止。遗传谱系追踪显示，SETD4+细胞在神经外胚层形成之前就出现了，并对大脑发育做出了贡献。在成人中，有条件地敲除Set4导致神经干细胞静止退出，在嗅球中产生新生的神经元，并有助于损伤的修复。然而，SETD4的长时间缺失导致NSC储备库耗尽或SETD4过表达导致NSCs静止进入，导致神经发生受抑。这项研究揭示了长寿、深度静止的神经干细胞的存在及其激活之外的神经遗传能力。SETD4标记的长寿命神经干细胞在成年小鼠的SVZ中处于深静止状态SETD4细胞起源于早期胚胎阶段并有助于脑发育SETD4的缺失导致NSCs的静止退出并促进神经发生在SetD4的持续缺失或过表达减少活跃的NSCs和神经发生在本文中，杨和他的同事通过SETD4的谱系追踪在小鼠脑室下区鉴定了一小部分长寿命的深静止NSCs。这些神经干细胞具有胚胎起源，并在进入静止状态之前对大脑发育做出贡献。这个静止的神经干细胞储存库一旦激活，就保留了神经发生和损伤修复的能力。
Cellular quiescence facilitates maintenance of neural stem cells (NSCs) and their subsequent regenerative functions in response to brain injury and aging. However, the specification and maintenance of NSCs in quiescence from embryo to adulthood remain largely unclear. Here, using Set domain-containing protein 4 (SETD4), an epigenetic determinant of cellular quiescence, we mark a small but long-lived NSC population in deep quiescence in the subventricular zone of adult murine brain. Genetic lineage tracing shows that SETD4+ cells appear before neuroectoderm formation and contribute to brain development. In the adult, conditional knockout of Setd4 resulted in quiescence exit of NSCs, generating newborn neurons in the olfactory bulb and contributing to damage repair. However, long period deletion of SETD4 lead to exhaustion of NSC reservoir or SETD4 overexpression caused quiescence entry of NSCs, leading to suppressed neurogenesis. This study reveals the existence of long-lived deep quiescent NSCs and their neurogenetic capacities beyond activation. SETD4 marked long-lived NSCs in deep quiescence in the SVZ of adult murine brains SETD4 cells originated in early embryonic stage and contribute to brain development Deletion of Setd4 resulted in quiescence exit of NSCs and facilitated neurogenesis Persist deletion or overexpression of Setd4 reduced active NSCs and neurogenesis In this article, Yang and colleagues identify a small population of long-lived deep quiescent NSCs in the subventricular zone of the murine brain with lineage tracing of SETD4. These NSCs possess embryonic origins and contribute to brain development before entering quiescence. This quiescent NSC reservoir preserves the capacity of neurogenesis and damage repair once activated.
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影响因子：
16.6
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影响因子：
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作者：
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