Enhanced lysosomal degradation maintains the quiescent state of neural stem cells

Taeko Kobayashi (), Wenhui Piao, Toshiya Takamura, Hiroshi Kori, Hitoshi Miyachi, Satsuki Kitano, Yumiko Iwamoto, Mayumi Yamada, Itaru Imayoshi, Seiji Shioda, Andrea Ballabio and Ryoichiro Kageyama ()
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Taeko Kobayashi: Kyoto University
Wenhui Piao: Kyoto University
Toshiya Takamura: Kyoto University
Hiroshi Kori: University of Tokyo
Hitoshi Miyachi: Kyoto University
Satsuki Kitano: Kyoto University
Yumiko Iwamoto: Kyoto University
Mayumi Yamada: Kyoto University
Itaru Imayoshi: Kyoto University
Seiji Shioda: Hoshi University
Andrea Ballabio: Telethon Institute of Genetics and Medicine
Ryoichiro Kageyama: Kyoto University

Nature Communications, 2019, vol. 10, issue 1, 1-14

Abstract: Abstract Quiescence is important for sustaining neural stem cells (NSCs) in the adult brain over the lifespan. Lysosomes are digestive organelles that degrade membrane receptors after they undergo endolysosomal membrane trafficking. Enlarged lysosomes are present in quiescent NSCs (qNSCs) in the subventricular zone of the mouse brain, but it remains largely unknown how lysosomal function is involved in the quiescence. Here we show that qNSCs exhibit higher lysosomal activity and degrade activated EGF receptor by endolysosomal degradation more rapidly than proliferating NSCs. Chemical inhibition of lysosomal degradation in qNSCs prevents degradation of signaling receptors resulting in exit from quiescence. Furthermore, conditional knockout of TFEB, a lysosomal master regulator, delays NSCs quiescence in vitro and increases NSC proliferation in the dentate gyrus of mice. Taken together, our results demonstrate that enhanced lysosomal degradation is an important regulator of qNSC maintenance.

Date: 2019
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DOI: 10.1038/s41467-019-13203-4

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