Autocrine Mfge8 Signaling Prevents Developmental Exhaustion of the Adult Neural Stem Cell Pool

Cell Stem Cell
Yi ZhouHongjun Song

Abstract

Adult neurogenesis, arising from quiescent radial-glia-like neural stem cells (RGLs), occurs throughout life in the dentate gyrus. How neural stem cells are maintained throughout development to sustain adult mammalian neurogenesis is not well understood. Here, we show that milk fat globule-epidermal growth factor (EGF) 8 (Mfge8), a known phagocytosis factor, is highly enriched in quiescent RGLs in the dentate gyrus. Mfge8-null mice exhibit decreased adult dentate neurogenesis, and furthermore, adult RGL-specific deletion of Mfge8 leads to RGL overactivation and depletion. Similarly, loss of Mfge8 promotes RGL activation in the early postnatal dentate gyrus, resulting in a decreased number of label-retaining RGLs in adulthood. Mechanistically, loss of Mfge8 elevates mTOR1 signaling in RGLs, inhibition of which by rapamycin returns RGLs to quiescence. Together, our study identifies a neural-stem-cell-enriched niche factor that maintains quiescence and prevents developmental exhaustion of neural stem cells to sustain continuous neurogenesis in the adult mammalian brain.

Citations

Sep 10, 2020·The FEBS Journal·Taeko Kobayashi, Ryoichiro Kageyama
Mar 31, 2019·Proceedings of the National Academy of Sciences of the United States of America·Jose L Nieto-GonzálezRafael Fernández-Chacón
Jun 20, 2019·Frontiers in Neuroscience·Cletus CheyuoPing Wang
Jun 20, 2019·Frontiers in Cell and Developmental Biology·Aixa V Morales, Helena Mira
Jul 28, 2020·Frontiers in Cell and Developmental Biology·Antonela BonafinaFernanda Ledda
Apr 17, 2020·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Lei ZhangJingjing Cai
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Aug 12, 2020·Mechanisms of Ageing and Development·Amanda J Audesse, Ashley E Webb
Nov 17, 2021·Neural Regeneration Research·Joshua D RieskampElizabeth D Kirby

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