Examination of neuroregulation in intestinal epithelium using stem cell differentiation-visualizing mice

2013 Fiscal Year Final Research Report

• Project/Area Number: 23590953
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Kansai Medical University
• Principal Investigator: HISHA Hiroko 関西医科大学, 医学部, 講師 (90151422)
• Co-Investigator(Kenkyū-buntansha): HOSAKA Naoki 関西医科大学, 医学部, 講師 (30388459) ; MAKI Masahiko 関西医科大学, 医学部, 講師 (80297001) ; KANDA Akira 関西医科大学, 医学部, 講師 (70375244)
• Project Period (FY): 2011 – 2013
• Keywords: 小腸 / 上皮幹細胞 / パネート細胞 / 神経伝達物質 / VIP / 神経線維 / オルガノイド

Research Abstract

Vasoactive intestinal peptide (VIP), a neurotransmitter, is released by the parasympathetic neurons in the small intestine. Epithelial stem cells (ESCs) reside at the epithelial layer of crypts in the small intestine and are directly intermingled with Paneth cells which provide a suitable environment for the ESCs.
In the present study, VIP-positive neurons were detected approximately under subepithelial mesenchymal cells. It was also found that VIP receptors (VPAC1R) were expressed on Paneth cells but not on the ESCs. When VIP was added to a three-dimensional organoid culture system of intestinal crypts, the formation of organoids was inhibited in a dose-dependent manner. It was previously reported that VPAC1R-knockout mice had the hyper-proliferative intestinal epithelium. From the result reported and the present findings, it is conceivable that VIP is a physiological neuroregulatory factor which regulates negatively the proliferation/differentiation of ESCs.

Research Products

• [Journal Article] Establishment of a Novel Lingual Organoid Culture System : Generation of Organoids Having Mature Keratinized Epithelium from Adult Epithelial Stem Cells (2013)
  • Author(s): Hiroko Hisha, Toshihiro Tanaka, Shohei Kanno, Yoko Tokuyama, Yoshihiro Komai, Shuichi Ohe, Hirotsugu Yanai, Taichi Omachi, and Hiroo Ueno
  • Journal Title: Scientific Reports Volume: 3 Pages: 3224
  • DOI: 10.1038/srep03224
  • Peer Reviewed
• [Presentation] 舌上皮細胞3次元培養システムの確立:舌上皮幹細胞からのオルガノイド形成 (2014)
  • Author(s): 比舍弘子, 田中敏宏, 菅野渉平, 徳山陽子, 駒井資弘, 大江秀一, 矢内洋次, 大町太一, 石垣和彦, 田中聖道, 厚海奈穂, 吉田真子, 熊野恵城, 上野博夫
  • Organizer: 第103回日本病理学会総会
  • Place of Presentation: 広島(ANAクラウンプラザホテル広島)
  • Year and Date: 2014-04-26
• [Presentation] 舌糸状乳頭角化上皮細胞の維持・再生を担う舌上皮幹細胞の同定 (2013)
  • Author(s): 田中敏宏, 駒井資弘, 矢内洋次, 大江秀一, 大町太一, 厚海奈穂, 菅野渉平, 吉田真子, 比舍弘子, 熊野恵城, 岡崎和一, 上野博夫
  • Organizer: 第72回日本癌学会
  • Place of Presentation: 横浜(パシフィコ横浜)
  • Year and Date: 2013-10-03
• [Presentation] 舌糸状乳頭角化上皮細胞の維持・再生を担う舌上皮幹細胞の同定 (2013)
  • Author(s): 田中敏宏, 駒井資弘, 徳山陽子, 大町太一, 矢内洋次, 大江秀一, 厚海奈穂, 菅野渉平, 比舍弘子, 岡崎和一, 上野博夫
  • Organizer: 第102回日本病理学会総会
  • Place of Presentation: 札幌(ロイトン札幌)
  • Year and Date: 2013-06-06
• [Presentation] Neuroregulation of Intestinal Epithelium by Neurotransmitters (2012)
  • Author(s): 比舍弘子, 上野博夫
  • Organizer: 第41回日本免疫学会総会
  • Place of Presentation: 神戸(神戸国際展示場)
  • Year and Date: 2012-12-05
• [Presentation] フローサイトメトリーによる多色細胞系譜マウスを背景に持つ遺伝子改変マウスの解析 (2012)
  • Author(s): 神田晃, 大江秀一, 矢内洋次, 田中敏宏, 駒井資弘, 大町太一, 徳山陽子, 西田真子, 山本真理, 槇政彦, 比舍弘子, 上野博夫
  • Organizer: 第22回日本サイトメトリー学会
  • Place of Presentation: 大阪(千里ライフサイエンスセンター)
  • Year and Date: 2012-06-29