SSBD - CREST-MC Paper - Kobayashi T et. al. (2019), Nat Commun 10(1), 5446

CREST MC: Kobayashi T et. al. (2019), Nat Commun 10(1), 5446

SSBD:database

189-Kobayashi-NSCsDyn

SSBD:repository

ssbd-repos-000189

CREST MC Teams

Imayoshi

CREST MC Groups

Imayoshi

Paper information

Taeko Kobayashi, Wenhui Piao, Toshiya Takamura, Hiroshi Kori, Hitoshi Miyachi, Satsuki Kitano, Yumiko Iwamoto, Mayumi Yamada, Itaru Imayoshi, Seiji Shioda, Andrea Ballabio, Ryoichiro Kageyama (2019) Enhanced lysosomal degradation maintains the quiescent state of neural stem cells., Nature communications, Volume 10, Number 1, pp. 5446

Electronic Published Date

Nov. 29, 2019, midnight

Published Date

2019 Nov 29

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.

PubMed Central ID

PMC6884460