Small intestinal stem cell identity is maintained with functional Paneth cells in heterotopically grafted epithelium onto the colon

Masayoshi Fukuda; Tomohiro Mizutani; Wakana Mochizuki; Taichi Matsumoto; Kengo Nozaki; Yuriko Sakamaki; Shizuko Ichinose; Yukinori Okada; Toshihiro Tanaka; Mamoru Watanabe; Tetsuya Nakamura

doi:10.1101/gad.245233.114

Small intestinal stem cell identity is maintained with functional Paneth cells in heterotopically grafted epithelium onto the colon

¹Department of Gastroenterology and Hepatology,
²Research Center for Medical and Dental Sciences,
³Department of Human Genetics and Disease Diversity,
⁴Bioresource Research Center,
⁵Department of Advanced Therapeutics for GI Diseases, Tokyo Medical and Dental University, 113-8519 Tokyo, Japan

Corresponding author: nakamura.gast{at}tmd.ac.jp

↵6 These authors contributed equally to this study.

Abstract

To develop stem cell therapy for small intestinal (SI) diseases, it is essential to determine whether SI stem cells in culture retain their tissue regeneration capabilities. By using a heterotopic transplantation approach, we show that cultured murine SI epithelial organoids are able to reconstitute self-renewing epithelia in the colon. When stably integrated, the SI-derived grafts show many features unique only to the SI but distinct from the colonic epithelium. Our study provides evidence that cultured adult SI stem cells could be a source for cell therapy of intestinal diseases, maintaining their identity along the gastrointestinal tract through an epithelium-intrinsic mechanism.

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Footnotes

Supplemental material is available for this article.
Article is online at http://www.genesdev.org/cgi/doi/10.1101/gad.245233.114.

Received May 19, 2014.
Accepted July 23, 2014.

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