Simultaneous real-time analysis of Paneth cell and intestinal stem cell response to interferon-γ by a novel stem cell niche tracking method

被引:11
作者
Yokoi, Yuki [1 ]
Adachi, Takahiro [2 ]
Sugimoto, Rina [3 ]
Kikuchi, Mani [1 ]
Ayabe, Tokiyoshi [1 ,3 ]
Nakamura, Kiminori [1 ,3 ]
机构
[1] Hokkaido Univ, Fac Adv Life Sci, Dept Cell Biol Sci, Innate Immun Lab,Kita Ku, Kita 21,Nishi 11, Sapporo, Hokkaido 0010021, Japan
[2] Tokyo Med & Dent Univ, Med Res Inst, Dept Immunol, Bunkyo Ku, 1-5-45 Yushima, Tokyo 1138510, Japan
[3] Hokkaido Univ, Grad Sch Life Sci, Innate Immun Lab, Kita Ku, Kita 21,Nishi 11, Sapporo, Hokkaido 0010021, Japan
基金
日本科学技术振兴机构; 日本学术振兴会;
关键词
Paneth cell; Intestinal stem cell; Stem cell niche; Interferon-gamma; Live imaging;
D O I
10.1016/j.bbrc.2021.01.050
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Paneth cells and Lgr5+ intestinal stem cells (Lgr5+ ISCs) constitute the stem cell niche and maintain small intestinal epithelial integrity by recognizing various niche factors derived from subepithelial cells and external antigens. Although it has been known that interferon-gamma (IFN-gamma), a Th1 cytokine, is associated with intestinal epithelial disruption during inflammation as a niche factor, dynamics of Paneth cells and Lgr5+ ISCs in response to IFN-gamma remain to be understood. Here we show that CAG-tdTomato;Lgr5-EGFP (CT-LE) mice generated in this study enable to identify Paneth cells and Lgr5+ ISCs separately by fluorescence signals. Lgr5+ ISCs underwent cell death a little earlier than Paneth cells in response to IFN-gamma by simultaneous tracking using CT-LE mice. In addition, the timing of cell death in most Paneth cells overlapped with Lgr5+ ISCs, suggesting that Paneth cell depletion is induced directly by IFN-gamma. Taken together, we established a novel simultaneous stem cell niche tracking method and clarified the involvement of both Paneth cells and Lgr5+ ISCs in stem cell niche damage induced by IFN-gamma, further contribute to understanding the mechanism for maintaining intestinal homeostasis by stem cell niche. (C) 2021 The Authors. Published by Elsevier Inc.
引用
收藏
页码:14 / 19
页数:6
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