ATOH1 is a master transcription factor for the secretory lineage differentiation of intestinal epithelial cells (IECs). However, the comprehensive contribution of ATOH1 secretory lineage IECs to the homeostasis, repair, and tumorigenesis of the intestinal epithelium remains uncertain. Through our ATOH1 cell-lineage tracing, we show here that a definite number of ATOH1 IECs retain stem cell properties and can form ATOH1IEC-derived clonal ribbons (ATOH1ICRs) under completely homeostatic conditions. Interestingly, colonic ATOH1 IECs appeared to exhibit their stem cell function more frequently compared with those of the small intestine. Consistently, the formation of ATOH1ICRs was significantly enhanced upon dextran sodium sulfate colitis-induced mucosal damage. In addition, colonic ATOH1 IECs acquired tumor stem cell-like properties in the azoxymethane-DSS tumor model. Our results reveal an unexpected contribution of colonic ATOH1 IECs to maintaining the stem cell population under both homeostatic and pathologic conditions and further illustrate the high plasticity of the crypt-intrinsic stem cell hierarchy.
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| http://dx.doi.org/10.1016/j.stemcr.2017.11.006 | DOI Listing |
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