Quiescence Exit of Tert(+) Stem Cells by Wnt/beta-Catenin Is Indispensable for Intestinal Regeneration
- Authors
- Suh, Han Na; Kim, Moon Jong; Jung, Youn-Sang; Lien, Esther M.; Jun, Sohee; Park, Jae-Il
- Issue Date
- Nov-2017
- Publisher
- CELL PRESS
- Keywords
- intestinal regeneration; intestinal stem cells; radiation; ROS-HIFs-Wnt2b; Tert; Wnt/β-catenin
- Citation
- CELL REPORTS, v.21, no.9, pp 2571 - 2584
- Pages
- 14
- Journal Title
- CELL REPORTS
- Volume
- 21
- Number
- 9
- Start Page
- 2571
- End Page
- 2584
- URI
- https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/63953
- DOI
- 10.1016/j.celrep.2017.10.118
- ISSN
- 2211-1247
- Abstract
- Fine control of stem cell maintenance and activation is crucial for tissue homeostasis and regeneration. However, the mechanism of quiescence exit of Tert(+) intestinal stem cells (ISCs) remains unknown. Employing a Tert knockin (Tert(TCE/+)) mouse model, we found that Tert(+) cells are long-term label-retaining self-renewing cells, which are partially distinguished from the previously identified +4 ISCs. Tert(+) cells become mitotic upon irradiation (IR) injury. Conditional ablation of Tert(+) cells impairs IR-induced intestinal regeneration but not intestinal homeostasis. Upon IR injury, Wnt signaling is specifically activated in Tert(+) cells via the ROS-HIFs-transactivated Wnt2b signaling axis. Importantly, conditional knockout of beta-catenin/Ctnnb1 in Tert(+) cells undermines IR-induced quiescence exit of Tert(+) cells, which subsequently impedes intestinal regeneration. Our results that Wnt-signaling-induced activation of Tert(+) ISCs is indispensable for intestinal regeneration unveil the underlying mechanism for how Tert(+) stem cells undergo quiescence exit upon tissue injury.
- Files in This Item
- There are no files associated with this item.
- Appears in
Collections - College of Natural Sciences > Department of Life Science > 1. Journal Articles
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.