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 (TertTCE/+) 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 β-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. Suh et al. define Tert+ cells as stem cells essential for intestinal regeneration and unveil how Tert+ intestinal stem cells escape from the quiescent state and undergo repopulation into progenitor cells upon tissue injury.
Original language | English (US) |
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Pages (from-to) | 2571-2584 |
Number of pages | 14 |
Journal | Cell Reports |
Volume | 21 |
Issue number | 9 |
DOIs | |
State | Published - Nov 28 2017 |
Keywords
- ROS-HIFs-Wnt2b
- Tert
- Wnt/β-catenin
- intestinal regeneration
- intestinal stem cells
- radiation
ASJC Scopus subject areas
- General Biochemistry, Genetics and Molecular Biology
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