Contribution of ATOH1+ Cells to the Homeostasis, Repair, and Tumorigenesis of the Colonic Epithelium.

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.

• Authors: Fumiaki Ishibashi, Hiromichi Shimizu, Toru Nakata, Satoru Fujii, Kohei Suzuki, Ami Kawamoto, Sho Anzai, Reiko Kuno, Sayaka Nagata, Go Ito, Tatsuro Murano, Tomohiro Mizutani, Shigeru Oshima, Kiichiro Tsuchiya, Tetsuya Nakamura, Mamoru Watanabe, Ryuichi Okamoto
• Journal: Stem cell reports (Stem Cell Reports) Vol. 10 Issue 1 Pg. 27-42 (01 09 2018) ISSN: 2213-6711 [Electronic] United States
• PMID: 29233556 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Chemical References

• Atoh1 protein, mouse
• Azo Compounds
• Basic Helix-Loop-Helix Transcription Factors
• Neoplasm Proteins
• azomethane

Topics

• Animals
• Azo Compounds (toxicity)
• Basic Helix-Loop-Helix Transcription Factors (genetics, metabolism)
• Cell Transformation, Neoplastic (chemically induced, genetics, metabolism, pathology)
• Colon (injuries, metabolism, pathology)
• Colonic Neoplasms (chemically induced, genetics, metabolism, pathology)
• Epithelial Cells (metabolism, pathology)
• Intestinal Mucosa (injuries, metabolism, pathology)
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Mice, Transgenic
• Neoplasm Proteins (genetics, metabolism)
• Neoplastic Stem Cells (metabolism, pathology)