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

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. Thro...

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Main 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
Format: Article
Language:English
Published: Elsevier 2018-01-01
Series:Stem Cell Reports
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Online Access:http://www.sciencedirect.com/science/article/pii/S2213671117304927
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author 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
author_facet 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
author_sort Fumiaki Ishibashi
collection DOAJ
description 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.
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spelling doaj.art-87734184b9144dfba2a2a9114587cdcd2022-12-21T23:07:41ZengElsevierStem Cell Reports2213-67112018-01-01101274210.1016/j.stemcr.2017.11.006Contribution of ATOH1+ Cells to the Homeostasis, Repair, and Tumorigenesis of the Colonic EpitheliumFumiaki Ishibashi0Hiromichi Shimizu1Toru Nakata2Satoru Fujii3Kohei Suzuki4Ami Kawamoto5Sho Anzai6Reiko Kuno7Sayaka Nagata8Go Ito9Tatsuro Murano10Tomohiro Mizutani11Shigeru Oshima12Kiichiro Tsuchiya13Tetsuya Nakamura14Mamoru Watanabe15Ryuichi Okamoto16Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, Tokyo 113-8519, JapanDepartment 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, USADepartment of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, Tokyo 113-8519, JapanDepartment of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, Tokyo 113-8519, JapanDepartment of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, Tokyo 113-8519, JapanDepartment of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, Tokyo 113-8519, JapanDepartment of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, Tokyo 113-8519, JapanDepartment of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, Tokyo 113-8519, JapanDepartment of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, Tokyo 113-8519, JapanDepartment 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, GermanyDepartment of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, Tokyo 113-8519, JapanDepartment of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, Tokyo 113-8519, JapanDepartment of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, Tokyo 113-8519, JapanDepartment of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, Tokyo 113-8519, JapanDepartment of Advanced Therapeutics in GI Diseases, Graduate School, Tokyo Medical and Dental University, Tokyo 113-8519, JapanDepartment of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, Tokyo 113-8519, JapanDepartment 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 authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2213671117304927Atoh1intestinal secretory cellplasticityde-differentiationintestinal stem cellcolonic inflammation
spellingShingle 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
Contribution of ATOH1+ Cells to the Homeostasis, Repair, and Tumorigenesis of the Colonic Epithelium
Stem Cell Reports
Atoh1
intestinal secretory cell
plasticity
de-differentiation
intestinal stem cell
colonic inflammation
title Contribution of ATOH1+ Cells to the Homeostasis, Repair, and Tumorigenesis of the Colonic Epithelium
title_full Contribution of ATOH1+ Cells to the Homeostasis, Repair, and Tumorigenesis of the Colonic Epithelium
title_fullStr Contribution of ATOH1+ Cells to the Homeostasis, Repair, and Tumorigenesis of the Colonic Epithelium
title_full_unstemmed Contribution of ATOH1+ Cells to the Homeostasis, Repair, and Tumorigenesis of the Colonic Epithelium
title_short Contribution of ATOH1+ Cells to the Homeostasis, Repair, and Tumorigenesis of the Colonic Epithelium
title_sort contribution of atoh1 cells to the homeostasis repair and tumorigenesis of the colonic epithelium
topic Atoh1
intestinal secretory cell
plasticity
de-differentiation
intestinal stem cell
colonic inflammation
url http://www.sciencedirect.com/science/article/pii/S2213671117304927
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