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Original Article

Exp Neurobiol 2019; 28(2): 229-246

Published online April 30, 2019

© The Korean Society for Brain and Neural Sciences

Autophagy Mediates Astrogenesis in Adult Hippocampal Neural Stem Cells

Shinwon Ha1,†, Seol-Hwa Jeong1,†, Kyungrim Yi1,†, Jamie Jeong-Min Chu1, Seolsong Kim1, Eun-Kyoung Kim1,2, and Seong-Woon Yu1,2*

1Department of Brain and Cognitive Sciences, Daegu Gyeongbuk Institute of Science and Technology (DGIST), Daegu 42988, Korea.

2Neurometabolomics Research Center, Daegu Gyeongbuk Institute of Science and Technology (DGIST), Daegu 42988, Korea.

Correspondence to: *To whom correspondence should be addressed.
TEL: 82-53-785-6113, FAX: 82-53-785-1209
These authors contributed equally to this work.

Received: October 17, 2018; Revised: March 6, 2019; Accepted: March 13, 2019

Neural stem cells (NSCs) have the ability to self-renew and differentiate into neurons, oligodendrocytes, and astrocytes. Highly dynamic nature of NSC differentiation requires the intimate involvement of catabolic processes such as autophagy. Autophagy is a major intracellular degradation pathway necessary for cellular homeostasis and remodeling. Autophagy is important for mammalian development and its role in neurogenesis has recently drawn much attention. However, little is known about how autophagy is associated with differentiation of NSCs into other neural lineages. Here, we report that autophagy plays a critical role in differentiation of adult rat hippocampal neural stem (HCN) cells into astrocytes. During differentiation, autophagy flux peaked at early time points, and remained high. Pharmacological or genetic suppression of autophagy by stable knockdown of Atg7, LC3 or CRISPR-Cas9-mediated knockout (KO) of p62 impaired astrogenesis, while reintroduction of p62 recovered astrogenesis in p62 KO HCN cells. Taken together, our findings suggest that autophagy plays a key role in astrogenesis in adult NSCs.

Graphical Abstract

Keywords: Adult stem cells, Astrocytes, Autophagy, Autophagy-related protein 7, Cell differentiation, Neural stem cells, Sequestosome-1 protein