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CREPT is required for murine stem cell maintenance during intestinal regeneration

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Listed:
  • 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)

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.

Suggested Citation

  • 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 & Zhijie Chang, 2021. "CREPT is required for murine stem cell maintenance during intestinal regeneration," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-020-20636-9
    DOI: 10.1038/s41467-020-20636-9
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