Simultaneous real-time analysis of Paneth cell and intestinal stem cell response to interferon-γ by a novel stem cell niche tracking method
Simultaneous real-time analysis of Paneth cell and intestinal stem cell response to interferon-γ by a novel stem cell niche tracking method
复制标题
通过新型干细胞生态位跟踪方法同时实时分析潘氏细胞和肠道干细胞对干扰素-γ的反应
DOI：
10.1016/j.bbrc.2021.01.050
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Nakamura K
中科院分区：
文献类型：
--
作者：
Yokoi Y;Adachi T;Sugimoto R;Kikuchi M;Ayabe T;Nakamura K
潘氏细胞和Lgr 5+肠干细胞（Lgr 5 + ISCs）通过识别来自上皮下细胞和外部抗原的各种生态位因子构成干细胞生态位并维持小肠上皮的完整性。虽然已经知道干扰素-γ（IFN-γ），一种Th 1细胞因子，作为一种生态位因子与炎症期间的肠上皮破坏相关，但是Paneth细胞和Lgr 5 + ISCs响应IFN-γ的动力学仍有待了解。这里我们展示了CAG-tdTomato;本研究中产生的Lgr 5-EGFP（CT-LE）小鼠能够通过荧光信号分别识别Paneth细胞和Lgr 5 + ISC。用CT-LE小鼠同时追踪法发现，IFN-γ诱导的Lgr 5 + ISCs比Paneth细胞早一点死亡。此外，大多数Paneth细胞中的细胞死亡时间与Lgr 5 + ISC重叠，表明Paneth细胞耗竭直接由IFN-γ诱导。综上所述，我们建立了一种新的同步干细胞生态位追踪方法，阐明了Paneth细胞和Lgr 5 + ISCs参与IFN-γ诱导的干细胞生态位损伤，进一步有助于理解干细胞生态位维持肠道稳态的机制。
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-γ (IFN-γ), 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-γ remain to be understood. Here we show thatCAG-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-γ by simultaneous tracking usingCT-LEmice. 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-γ. 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-γ, further contribute to understanding the mechanism for maintaining intestinal homeostasis by stem cell niche.