期刊
CELL REPORTS
卷 35, 期 1, 页码 -出版社
CELL PRESS
DOI: 10.1016/j.celrep.2021.108949
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资金
- National Institutes of Health (NIH) [R01CA200893]
- Swedish Research Council (Vetenskapsra det [V]) grant [2015-00656]
- Swedish Society for Medical Research (Svenska Sallskapet for Medicinsk Forskning) grant [P17-0060]
- NIH [5U01AI095545-08]
- VR [2018-02278]
- Swedish Research Council [2015-00656, 2018-02278] Funding Source: Swedish Research Council
- Forte [2015-00656] Funding Source: Forte
- Vinnova [2018-02278] Funding Source: Vinnova
The proliferation of colonic stem cells (CSCs) is mediated by redox-dependent activation of epidermal growth factor receptor (EGFR) signaling via NADPH oxidase 1 (NOX1). NOX1 expression is CSC-specific and regulated by Toll-like receptor activation in response to the microbiota, linking CSC proliferation with the presence of bacterial components in the crypt.
The colon epithelium is a primary point of interaction with the microbiome and is regenerated by a few rapidly cycling colonic stem cells (CSCs). CSC self-renewal and proliferation are regulated by growth factors and the presence of bacteria. However, the molecular link connecting the diverse inputs that maintain CSC homeostasis remains largely unknown. We report that CSC proliferation is mediated by redox-dependent activation of epidermal growth factor receptor (EGFR) signaling via NADPH oxidase 1 (NOX1). NOX1 expression is CSC specific and is restricted to proliferative CSCs. In the absence of NOX1, CSCs fail to generate ROS and have a reduced proliferation rate. NOX1 expression is regulated by Toll-like receptor activation in response to the microbiota and serves to link CSC proliferation with the presence of bacterial components in the crypt. The TLR-NOX1-EGFR axis is therefore a critical redox signaling node in CSCs facilitating the quiescent-proliferation transition and responds to the microbiome to maintain colon homeostasis.
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