caa a22 4500 445889187 CHVBK 20180317145610.0 cr unu---uuuuu 170323e20110201xx s 000 0 eng 10.1007/s00535-010-0346-x doi (NATIONALLICENCE)springer-10.1007/s00535-010-0346-x Longitudinal cell formation in the entire human small intestine is correlated with the localization of Hath1 and Klf4 [Elektronische Daten] [Michiko Iwasaki, Kiichiro Tsuchiya, Ryuichi Okamoto, Xiu Zheng, Yoshihito Kano, Eiko Okamoto, Eriko Okada, Akihiro Araki, Shinji Suzuki, Naoya Sakamoto, Keisuke Kitagaki, Takumi Akashi, Yoshinobu Eishi, Tetsuya Nakamura, Mamoru Watanabe] Background: Double balloon endoscopy (DBE) enables the observation and collection of viable specimens from the entire intestine, thereby allowing more detailed investigation of how the structure and function of the human small intestine are regulated. The present study aimed to elucidate the regulation of cell formation in the human small intestine using biopsy specimens collected from an entire individual small intestine by DBE. Methods: The expression and the localization of representative genes for the differentiation program were analyzed in the entire small intestine of 10 patients. The functional correlation between Hath1 and Klf4 was analyzed in an intestinal cell line by using a Tet-On system. Results: In longitudinal cell formation in the small intestine, it was shown that goblet cells, but not Paneth cells, increased toward the ileum in each individual small intestine. Immunohistochemistry showed that Hath1-expressing cells migrated from the base of the crypt to the top of the villi in the terminal ileum, while Klf4-expressing cells migrated from the top of the villus, resulting in the colocalization of Hath1 and Klf4 in the terminal ileum. Coexpression of Hath1 and Klf4 upregulated the expression of phenotypic genes for goblet cells following the downregulation of those for Paneth cells. Conclusions: Using mapping biopsy by DBE, we have demonstrated, for the first time, the molecular basis of the villus structure in the entire human small intestine in vivo. The present study showed that longitudinal cell formation was regulated by the colocalization of Hath1 and Klf4 that converted Paneth cell differentiation into goblet cell differentiation. Springer, 2010 Double balloon endoscopy nationallicence Goblet cells nationallicence Paneth cells nationallicence Hath1 nationallicence Atoh1 nationallicence Iwasaki Michiko Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, 113-8519, Tokyo, Japan aut Tsuchiya Kiichiro Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, 113-8519, Tokyo, Japan aut Okamoto Ryuichi Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, 113-8519, Tokyo, Japan aut Zheng Xiu Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, 113-8519, Tokyo, Japan aut Kano Yoshihito Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, 113-8519, Tokyo, Japan aut Okamoto Eiko Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, 113-8519, Tokyo, Japan aut Okada Eriko Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, 113-8519, Tokyo, Japan aut Araki Akihiro Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, 113-8519, Tokyo, Japan aut Suzuki Shinji Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, 113-8519, Tokyo, Japan aut Sakamoto Naoya Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, 113-8519, Tokyo, Japan aut Kitagaki Keisuke Department of Pathology, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan aut Akashi Takumi Department of Pathology, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan aut Eishi Yoshinobu Department of Pathology, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan aut Nakamura Tetsuya Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, 113-8519, Tokyo, Japan aut Watanabe Mamoru Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, 113-8519, Tokyo, Japan aut Journal of Gastroenterology Springer Japan 46/2(2011-02-01), 191-202 0944-1174 46:2<191 2011 46 535 https://doi.org/10.1007/s00535-010-0346-x text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00535-010-0346-x text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Iwasaki Michiko Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, 113-8519, Tokyo, Japan aut NATIONALLICENCE 700 1- Tsuchiya Kiichiro Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, 113-8519, Tokyo, Japan aut NATIONALLICENCE 700 1- Okamoto Ryuichi Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, 113-8519, Tokyo, Japan aut NATIONALLICENCE 700 1- Zheng Xiu Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, 113-8519, Tokyo, Japan aut NATIONALLICENCE 700 1- Kano Yoshihito Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, 113-8519, Tokyo, Japan aut NATIONALLICENCE 700 1- Okamoto Eiko Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, 113-8519, Tokyo, Japan aut NATIONALLICENCE 700 1- Okada Eriko Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, 113-8519, Tokyo, Japan aut NATIONALLICENCE 700 1- Araki Akihiro Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, 113-8519, Tokyo, Japan aut NATIONALLICENCE 700 1- Suzuki Shinji Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, 113-8519, Tokyo, Japan aut NATIONALLICENCE 700 1- Sakamoto Naoya Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, 113-8519, Tokyo, Japan aut NATIONALLICENCE 700 1- Kitagaki Keisuke Department of Pathology, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan aut NATIONALLICENCE 700 1- Akashi Takumi Department of Pathology, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan aut NATIONALLICENCE 700 1- Eishi Yoshinobu Department of Pathology, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan aut NATIONALLICENCE 700 1- Nakamura Tetsuya Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, 113-8519, Tokyo, Japan aut NATIONALLICENCE 700 1- Watanabe Mamoru Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, 113-8519, Tokyo, Japan aut NATIONALLICENCE 773 0- Journal of Gastroenterology Springer Japan 46/2(2011-02-01), 191-202 0944-1174 46:2<191 2011 46 535 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer