Retinoic Acid Is Required for Neural Stem and Progenitor Cell Proliferation in the Adult Hippocampus.
Retinoic Acid Is Required for Neural Stem and Progenitor Cell Proliferation in the Adult Hippocampus.
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DOI：
10.1016/j.stemcr.2018.04.024
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发表时间：
2018-06-05
影响因子：
5.9
通讯作者：
Siegenthaler JA
中科院分区：
文献类型：
--
作者：
Mishra S;Kelly KK;Rumian NL;Siegenthaler JA
神经干细胞和前体细胞（NSPC）在啮齿动物成体海马中的增殖是维持干细胞群和产生新神经元的必要条件。视黄酸（RA）信号与成人海马神经发生的调节有关，但其在控制NSPC行为中的确切作用尚未得到研究。我们发现RA信号在所有海马NSPC亚型中均存在，抑制RA合成或信号传导可通过取消细胞周期动力学和细胞周期调节因子显著降低NSPC增殖。RA信号通过缺氧诱导因子-1α (HIF1α)控制NSPC增殖，HIF1α的稳定与RA信号的破坏可以防止NSPC缺陷。这些研究表明，RA信号在海马NSPCs中的细胞自主作用，大大拓宽了RA的功能，超出了其在神经元分化中的作用。RA合成的系统性减少损害了NSPC的增殖和神经发生HIF1α在RA的下游调节NSPC的s期再进入和细胞周期基因，RA信号是NSPC正常增殖所需的细胞自主信号。Mishra及其同事通过缺氧诱导因子-1α确定了维甲酸（RA）信号在成人海马神经干和祖细胞（NSPC）增殖中的关键作用。利用RA报告小鼠和成年NSPCs中RA信号的条件破坏，作者发现成年NSPCs中的RA信号和NSPC中的RA信号是正常增殖行为所必需的。
Neural stem and precursor cell (NSPC) proliferation in the rodent adult hippocampus is essential to maintain stem cell populations and produce new neurons. Retinoic acid (RA) signaling is implicated in regulation of adult hippocampal neurogenesis, but its exact role in control of NSPC behavior has not been examined. We show RA signaling in all hippocampal NSPC subtypes and that inhibition of RA synthesis or signaling significantly decreases NSPC proliferation via abrogation of cell-cycle kinetics and cell-cycle regulators. RA signaling controls NSPC proliferation through hypoxia inducible factor-1α (HIF1α), where stabilization of HIF1α concurrent with disruption of RA signaling can prevent NSPC defects. These studies demonstrate a cell-autonomous role for RA signaling in hippocampal NSPCs that substantially broadens RA's function beyond its well-described role in neuronal differentiation. Retinoic acid (RA) signaling in mouse hippocampal neural stem and progenitors (NSPCs) Systemic reduction in RA synthesis impairs NSPC proliferation and neurogenesis HIF1α acts downstream of RA to regulate NSPC S-phase re-entry and cell-cycle genes RA signaling is required cell autonomously in NSPCs for normal proliferation In this article, Mishra and colleagues identify a critical role for retinoic acid (RA) signaling in adult hippocampal neural stem and progenitor cell (NSPC) proliferation via hypoxia inducible factor-1α. Using RA reporter mice and conditional disruption of RA signaling in adult NSPCs, the authors identify RA signaling in adult NSPCs and NSPC RA signaling is required for normal proliferative behavior.
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