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Cell Rep. 2017 Nov 28;21(9):2571-2584. doi: 10.1016/j.celrep.2017.10.118.

Quiescence Exit of Tert+ Stem Cells by Wnt/β-Catenin Is Indispensable for Intestinal Regeneration.

Author information

1
Department of Experimental Radiation Oncology, Division of Radiation Oncology, The University of Texas, MD Anderson Cancer Center, Houston, TX 77030, USA.
2
Department of Experimental Radiation Oncology, Division of Radiation Oncology, The University of Texas, MD Anderson Cancer Center, Houston, TX 77030, USA; Graduate School of Biomedical Sciences, The University of Texas, MD Anderson Cancer Center, Houston, TX 77030, USA; Program in Genes and Development, The University of Texas MD, Anderson Cancer Center, Houston, TX 77030, USA. Electronic address: jaeil@mdanderson.org.

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.

KEYWORDS:

ROS-HIFs-Wnt2b; Tert; Wnt/β-catenin; intestinal regeneration; intestinal stem cells; radiation

PMID:
29186692
PMCID:
PMC5726811
DOI:
10.1016/j.celrep.2017.10.118
[Indexed for MEDLINE]
Free PMC Article

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