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CREPT is required for murine stem cell maintenance during intestinal regeneration

Liu Yang, Haiyan Yang, Yunxiang Chu, Yunhao Song, Lidan Ding, Bingtao Zhu, Wanli Zhai, Xuning Wang, Yanshen Kuang, Fangli Ren, Baoqing Jia, Wei Wu, Xiongjun Ye (), Yinyin Wang () and Zhijie Chang ()
Additional contact information
Liu Yang: Tsinghua University
Haiyan Yang: Tsinghua University
Yunxiang Chu: Emergency General Hospital
Yunhao Song: Tsinghua University
Lidan Ding: Tsinghua University
Bingtao Zhu: Tsinghua University
Wanli Zhai: Tsinghua University
Xuning Wang: Chinese PLA General Hospital
Yanshen Kuang: Chinese PLA General Hospital
Fangli Ren: Tsinghua University
Baoqing Jia: Chinese PLA General Hospital
Wei Wu: Tsinghua University
Xiongjun Ye: Peking University People’s Hospital
Yinyin Wang: Tsinghua University
Zhijie Chang: Tsinghua University

Nature Communications, 2021, vol. 12, issue 1, 1-13

Abstract: Abstract Intestinal stem cells (ISCs) residing in the crypts are critical for the continual self-renewal and rapid recovery of the intestinal epithelium. The regulatory mechanism of ISCs is not fully understood. Here we report that CREPT, a recently identified tumor-promoting protein, is required for the maintenance of murine ISCs. CREPT is preferably expressed in the crypts but not in the villi. Deletion of CREPT in the intestinal epithelium of mice (Vil-CREPTKO) results in lower body weight and slow migration of epithelial cells in the intestine. Vil-CREPTKO intestine fails to regenerate after X-ray irradiation and dextran sulfate sodium (DSS) treatment. Accordingly, the deletion of CREPT decreases the expression of genes related to the proliferation and differentiation of ISCs and reduces Lgr5+ cell numbers at homeostasis. We identify that CREPT deficiency downregulates Wnt signaling by impairing β-catenin accumulation in the nucleus of the crypt cells during regeneration. Our study provides a previously undefined regulator of ISCs.

Date: 2021
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DOI: 10.1038/s41467-020-20636-9

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