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

Yi Zhou, Allison M. Bond, Jamie E. Shade, Yunhua Zhu, Chung ha O. Davis, Xinyuan Wang, Yijing Su, Ki Jun Yoon, Alexander T. Phan, William J. Chen, Justin H. Oh, Nicholas Marsh-Armstrong, Kamran Atabai, Guo li Ming, Hongjun Song

Research output: Contribution to journalArticle

18 Scopus citations

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. Zhou et al. identify Mfge8, traditionally known for its role in phagocytosis, as a neural-stem-cell-enriched niche factor that maintains the neural stem cell pool in the dentate gyrus during early postnatal development and in adulthood by promoting neural stem cell quiescence.

Original languageEnglish (US)
Pages (from-to)444-452.e4
JournalCell Stem Cell
Volume23
Issue number3
DOIs
StatePublished - Sep 6 2018
Externally publishedYes

Keywords

  • adult neural stem cells
  • hippocampus
  • Mfge8
  • mTOR
  • neurogenesis
  • PTEN
  • quiescence
  • RGL

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Cell Biology

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  • Cite this

    Zhou, Y., Bond, A. M., Shade, J. E., Zhu, Y., Davis, C. H. O., Wang, X., Su, Y., Yoon, K. J., Phan, A. T., Chen, W. J., Oh, J. H., Marsh-Armstrong, N., Atabai, K., Ming, G. L., & Song, H. (2018). Autocrine Mfge8 Signaling Prevents Developmental Exhaustion of the Adult Neural Stem Cell Pool. Cell Stem Cell, 23(3), 444-452.e4. https://doi.org/10.1016/j.stem.2018.08.005