Identification of Fate Determinants in Human Small and Large Intestine
Project/Area Number |
21K15918
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Research Category |
Grant-in-Aid for Early-Career Scientists
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Allocation Type | Multi-year Fund |
Review Section |
Basic Section 53010:Gastroenterology-related
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Research Institution | Tokyo Medical and Dental University |
Principal Investigator |
Shuji Hibiya 東京医科歯科大学, 医学部附属病院, 特任助教 (20801963)
|
Project Period (FY) |
2021-04-01 – 2023-03-31
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Project Status |
Completed (Fiscal Year 2022)
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Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2022: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2021: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
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Keywords | 小腸大腸形質転換 / 形質転換 / 大腸・小腸化 / 機能補完 / 大腸化 |
Outline of Research at the Start |
腸管は小腸と大腸に分類されますが機能が異なります。炎症性腸疾患や腫瘍により腸管を大幅に切除されるとその機能が落ちるため苦しむことが多いですがその根本的な治療は存在しません。また小腸と大腸上皮の細胞構成が異なることでその機能の差に反映されますが、小腸と大腸の違いを制御する機構は明らかとされていません。そこで本研究では小腸と大腸の運命分岐機構を解明することで、小腸上皮の大腸化及び大腸上皮の小腸化を目指します。一旦切除された腸管を移植や再生医療にて補完する方法は現時点で非常に困難であることから、自己の類似臓器を目的の臓器に転換して機能を補完するという概念は将来的な医療応用での実現を期待できます。
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Outline of Final Research Achievements |
This study aims to elucidate the mechanism of fate divergence between small and large intestine, and to convert small intestinal epithelium into colon and colonic epithelium into small intestine. We aimed to extract differences between small and large intestinal epithelium by making full use of small and large intestinal endoscopic specimens and small and large intestinal organoids from the same individuals, and to identify fate branching genes related to the regulation of differentiation. We analyzed existing biopsy specimens and primary cultured cells to extract genes specifically expressed in the small and large intestine. Candidate genes were examined using specimens from different individuals, and one candidate gene that was common among different individuals was identified. The identified gene is being forced to be expressed in colon organoids by lentivirus to see if it acquires the small intestinal trait.
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Academic Significance and Societal Importance of the Research Achievements |
臓器再生に関するこれまでの研究は、ES細胞やiPS細胞などの多能性幹細胞から臓器を形 成する、組織幹細胞から臓器に分化させる、ブタなど動物内にヒト臓器を作成する、などが検討されているが、一方でヒト体内に存在する臓器を別の臓器に転換するという概念を前提とした研究は少ない。本研究の成果により小腸と大腸への運命制御機構を解明することにより、ヒト体内臓器転換による機能補完という新規治療への概念を提唱することが期待できる。
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Report
(3 results)
Research Products
(4 results)
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[Journal Article] Mucosal healing of small intestinal stricture is associated with improved prognosis post-dilation in Crohn's disease2022
Author(s)
Shuji Hibiya, Kazuo Ohtsuka, Kento Takenaka, Ami Kawamoto, Yusuke Matsuyama, Yumi Udagawa, Maiko Motobayashi, Hiromichi Shimizu, Toshimitsu Fujii, Eiko Saito, Masakazu Nagahori, Ryuichi Okamoto, Mamoru Watanabe
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Journal Title
BMC Gastroenterol.
Volume: 22
Issue: 1
Pages: 218-218
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Deep neural network for video colonoscopy of ulcerative colitis: a cross-sectional study2022
Author(s)
Kento Takenaka, Toshimitsu Fujii, Ami Kawamoto, Kohei Suzuki, Hiromichi Shimizu, Chiaki Maeyashiki, Osamu Yamaji, Maiko Motobayashi, Akira Igarashi, Ryoichi Hanazawa, Shuji Hibiya, Masakazu Nagahori, Eiko Saito, Ryuichi Okamoto, Kazuo Ohtsuka, Mamoru Watanabe
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Journal Title
Lancet Gastroenterol Hepatol
Volume: 7
Issue: 3
Pages: 230-237
DOI
Related Report
Peer Reviewed / Open Access
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