Analysis of intestinal mucosal repair by Notch-activated stem cells

Notch激活干细胞对肠粘膜修复的分析

• 批准号: 23790777
• 负责人: OKAMOTO Ryuichi
• 金额: $ 2.75万
• 依托单位: Tokyo Medical and Dental University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23790777/
• 关键词: 炎症性腸疾患; Notchシグナル; 腸管上皮; 上皮幹細胞; 粘膜再生; 腸管上皮初代培養; オルガノイド; Notch活性化; 細胞移植

Through our studies aimed to develop a primary culture system of the intestinal epithelial cells, in which Notch-activated stem cell can be easily visualized, we succeeded to establish a culture method using the LGR5-EGFP mice. Using those mice, we found that the intestinal organoids that were maintained in our culture method contains high number of stem cells. In addition, transplantation of those organiods to a colitic mice model resulted in re-construction of the damaged epithelia by the organoids, which was maintained for a sustained time period. These results establish the basis for cell transplantation-mediated regeneration therapy for intestinal diseases.

通过我们的研究，旨在开发肠上皮细胞的原发性培养系统，其中很容易看到Notch激活的干细胞，我们成功地使用LGR5-EGFP小鼠建立了一种培养方法。使用那些小鼠，我们发现在我们的培养方法中维持的肠道器可以包含大量的干细胞。此外，将这些有机体移植到colitic小鼠模型中导致细胞器重建了受损的上皮，该细节持续的时间很长。这些结果为细胞移植介导的肠道疾病的再生疗法的基础建立了基础。

项目成果

Notch pathway and TNF-a synergistically up-regulates OLFM4 expression in the inflamed mucosa of the human intestine.

Notch 通路和 TNF-a 协同上调人肠道发炎粘膜中 OLFM4 的表达。

• 作者: Okamoto R;Murano T;Watanabe M et al
• 通讯作者: Watanabe M et al

Establishment of novel bio-screening methods using cultured intestinal epithelial cells

利用培养的肠上皮细胞建立新型生物筛选方法

• 发表时间: 2012
• 作者: Ryuichi Okamoto;Morio-AkiyamaJunko;Hiromichi Shimizu;Tatsuro Murano;Go Ito;Satoru Fujii;Kiichiro Tsuchiya;Tetsuya Nakamura;Mamoru Watanabe;Okamoto R
• 通讯作者: Okamoto R

The acquisition of cancer stemness in colon cancer by the Atoh1 protein stabilization.

通过 Atoh1 蛋白稳定化获得结肠癌的癌症干性。

• 作者: Kano Y; Okamoto R;Nakamura T;Watanabe M et al
• 通讯作者: Watanabe M et al

Flagellin response via TLR5 on basolateral membrane of primary intestinal epithelial cells is regulated by Notch signaling.

原代肠上皮细胞基底外侧膜上 TLR5 的鞭毛蛋白反应受 Notch 信号传导调节。

• 作者: Tsuchiya K;Okamoto R;Nakamura T;Watanabe M et al
• 通讯作者: Watanabe M et al

Notch signaling regulates expression of Gelsolin superfamily genes, Gelsolin and Scinderin, and promotes re-assembly of actin cytoskelton in human intestinal epithelial cells

Notch信号调节凝溶胶蛋白超家族基因、凝溶胶蛋白和Scinderin的表达，并促进人肠上皮细胞中肌动蛋白细胞骨架的重新组装

• 发表时间: 2012
• 作者: Ryuichi Okamoto,Tatsuro Murano;Go Ito;Satoru Fujii;Hiromichi Shimizu;Kiichiro Tsuchiya;Tetsuya Nakamura;Mamoru Watanabe
• 通讯作者: Mamoru Watanabe