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

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

doi:10.1016/j.stemcr.2017.11.006

Stem Cell Reports (Jan 2018)

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

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

Affiliations

Fumiaki Ishibashi: Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, Tokyo 113-8519, Japan
Hiromichi Shimizu: Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, Tokyo 113-8519, Japan; Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA
Toru Nakata: Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, Tokyo 113-8519, Japan
Satoru Fujii: Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, Tokyo 113-8519, Japan
Kohei Suzuki: Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, Tokyo 113-8519, Japan
Ami Kawamoto: Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, Tokyo 113-8519, Japan
Sho Anzai: Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, Tokyo 113-8519, Japan
Reiko Kuno: Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, Tokyo 113-8519, Japan
Sayaka Nagata: Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, Tokyo 113-8519, Japan
Go Ito: Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, Tokyo 113-8519, Japan; Institute of Clinical Molecular Biology, Christian-Albrechts-University Kiel, 24118 Kiel, Germany
Tatsuro Murano: Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, Tokyo 113-8519, Japan
Tomohiro Mizutani: Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, Tokyo 113-8519, Japan
Shigeru Oshima: Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, Tokyo 113-8519, Japan
Kiichiro Tsuchiya: Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, Tokyo 113-8519, Japan
Tetsuya Nakamura: Department of Advanced Therapeutics in GI Diseases, Graduate School, Tokyo Medical and Dental University, Tokyo 113-8519, Japan
Mamoru Watanabe: Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, Tokyo 113-8519, Japan
Ryuichi Okamoto: Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, Tokyo 113-8519, Japan; Center for Stem Cell and Regenerative Medicine, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan; Corresponding author

DOI: https://doi.org/10.1016/j.stemcr.2017.11.006
Journal volume & issue: Vol. 10, no. 1
pp. 27 – 42

Abstract

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Summary: 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.

Published in Stem Cell Reports

ISSN: 2213-6711 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Medicine (General); Science: Biology (General)
Website: http://www.cell.com/stem-cell-reports/home

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