RRC ID 49642
Author Ishibashi F, Shimizu H, Nakata T, Fujii S, Suzuki K, Kawamoto A, Anzai S, Kuno R, Nagata S, Ito G, Murano T, Mizutani T, Oshima S, Tsuchiya K, Nakamura T, Watanabe M, Okamoto R.
Title Contribution of ATOH1+ Cells to the Homeostasis, Repair, and Tumorigenesis of the Colonic Epithelium.
Journal Stem Cell Reports
Abstract 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 ATOH1+IEC-derived clonal ribbons (ATOH1+ICRs) 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 ATOH1+ICRs 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.
Volume 10(1)
Pages 27-42
Published 2018-1-9
DOI 10.1016/j.stemcr.2017.11.006
PII S2213-6711(17)30492-7
PMID 29233556
PMC PMC5768891
MeSH Animals Azo Compounds / toxicity Basic Helix-Loop-Helix Transcription Factors / genetics Basic Helix-Loop-Helix Transcription Factors / metabolism* Cell Transformation, Neoplastic / chemically induced Cell Transformation, Neoplastic / genetics Cell Transformation, Neoplastic / metabolism* Cell Transformation, Neoplastic / pathology Colon / injuries Colon / metabolism* Colon / pathology Colonic Neoplasms / chemically induced Colonic Neoplasms / genetics Colonic Neoplasms / metabolism* Colonic Neoplasms / pathology Epithelial Cells / metabolism* Epithelial Cells / pathology Intestinal Mucosa / injuries Intestinal Mucosa / metabolism* Intestinal Mucosa / pathology Mice Mice, Inbred BALB C Mice, Nude Mice, Transgenic Neoplasm Proteins / genetics Neoplasm Proteins / metabolism* Neoplastic Stem Cells / metabolism* Neoplastic Stem Cells / pathology
IF 6.032
Times Cited 15
Mice RBRC01872