Endothelin-1 signaling maintains glial progenitor proliferation in the postnatal subventricular zone
Endothelin-1 signaling maintains glial progenitor proliferation in the postnatal subventricular zone
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DOI：
10.1038/s41467-020-16028-8
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发表时间：
2020-05-01
影响因子：
16.6
通讯作者：
Gallo, Vittorio
中科院分区：
文献类型：
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作者：
Adams, Katrina L.;Riparini, Giulia;Gallo, Vittorio
在出生后早期脑室下区（SVZ）调节神经发育过程的信号分子对正常的大脑发育至关重要，但仍然缺乏研究。在这里，我们报道了内皮素-1 (ET-1)，出生后SVZ的分子成分，通过Notch信号以自分泌方式促进放射状胶质细胞的维持和增殖。ET-1信号的缺失增加了发育中的SVZ的神经发生，减少了少突胶质祖细胞增殖（OPC），从而改变了干细胞生态位的细胞输出。我们还发现ET-1是成年小鼠SVZ脱髓鞘后神经干细胞和OPC增殖增加所必需的。最后，组织蛋白酶a相关性动脉病变合并中风和脑白质病患者SVZ中高水平的ET-1与SVZ OPCs数量增加相关，表明ET-1作为神经胶质祖细胞增殖调节因子的作用可能在人类中保守。因此，ET-1信号为促进svz介导的细胞修复提供了一个潜在的新治疗靶点。内皮素-1 （ET-1）是一种血管收缩分子，也存在于发育和损伤的中枢神经系统中。作者发现ET-1存在于出生后脑室下区，并调节放射状胶质细胞和少突胶质细胞祖细胞的维持和增殖。
Signaling molecules that regulate neurodevelopmental processes in the early postnatal subventricular zone (SVZ) are critical for proper brain development yet remain poorly characterized. Here, we report that Endothelin-1 (ET-1), a molecular component of the postnatal SVZ, promotes radial glial cell maintenance and proliferation in an autocrine manner via Notch signaling. Loss of ET-1 signaling increases neurogenesis and reduces oligodendrocyte progenitor cell proliferation (OPC) in the developing SVZ, thereby altering cellular output of the stem cell niche. We also show that ET-1 is required for increased neural stem cell and OPC proliferation in the adult mouse SVZ following demyelination. Lastly, high levels of ET-1 in the SVZ of patients with Cathepsin A-related arteriopathy with strokes and leukoencephalopathy correlate with an increased number of SVZ OPCs, suggesting ET-1's role as a regulator of glial progenitor proliferation may be conserved in humans. ET-1 signaling therefore presents a potential new therapeutic target for promoting SVZ-mediated cellular repair. Endothelin-1 (ET-1) is a vasoconstrictor molecule that is also present in the developing and injured CNS. Here the authors show that ET-1 is present in the postnatal subventricular zone and acts to regulate maintenance and proliferation of radial glial cells and oligodendrocyte progenitor cells.