Mist1+ gastric isthmus stem cells are regulated by Wnt5a and expand in response to injury and inflammation in mice.
Mist1+ gastric isthmus stem cells are regulated by Wnt5a and expand in response to injury and inflammation in mice.
复制标题
MIST1+胃静脉干细胞受WNT5A调节，并因小鼠的损伤和炎症而扩展。
DOI：
10.1136/gutjnl-2020-320742
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发表时间：
2021-04
期刊：
影响因子：
24.5
通讯作者：
Wang, Timothy C.
中科院分区：
文献类型：
--
作者：
Nienhuser, Henrik;Kim, Woosook;Malagola, Ermanno;Ruan, Tuo;Valenti, Giovanni;Middelhoff, Moritz;Bass, Adam;Der, Channing J.;Hayakawa, Yoku;Wang, Timothy C.
胃上皮持续更新。位于胃峡部的胃体上皮干细胞是组织自我更新的来源。我们最近确定了转录因子Mist 1作为这种可引起癌症的体干细胞群的标志物。本文的目的是研究Mist 1+干细胞在胃损伤和炎症反应中的调节作用。我们在两种损伤和炎症模型中使用Mist 1CreERT;R26-Tdtomato小鼠：乙酸诱导的溃疡和猫螺杆菌感染。我们分析了早期（7- 30天）和晚期（30- 90天）时间点的谱系追踪。使用MistlCreERT;R26-Tdtomato; Lgr 5DTR-eGFP小鼠消融基底体Lgr 5+细胞群。体质性和条件性Wnt 5a敲除小鼠用于研究Wnt 5a在伤口修复和Mist 1+干细胞谱系追踪中的作用。在两种胃损伤模型中，与正常状态相比，Mist 1+峡部干细胞更快速地增殖并追踪整个胃腺。在再生组织中，被追踪的胃主细胞的数量显著减少，并且Lgr 5+主细胞的消融不影响Mist 1衍生的谱系追踪和组织再生。Wnt 5a基因缺失损害了胃峡部的增殖和Mist 1+干细胞的谱系追踪类似地，Wnt 5a的主要来源先天淋巴样细胞（ILC 2）的耗竭也导致增殖减少和Mist 1+峡部细胞示踪。胃Mist 1+峡部细胞是再生腺体的主要供应者，并且部分通过Wnt 5a途径被激活。
The gastric epithelium undergoes continuous turnover. Corpus epithelial stem cells located in the gastric isthmus serve as a source of tissue self-renewal. We recently identified the transcription factor Mist1 as a marker for this corpus stem cell population that can give rise to cancer. The aim here was to investigate the regulation of the Mist1+ stem cells in the response to gastric injury and inflammation. We used Mist1CreERT;R26-Tdtomato mice in two models of injury and inflammation: the acetic acid-induced ulcer and infection with Helicobacter felis. We analyzed lineage tracing at both early (7–30d) and late (30–90d) time points. Mist1CreERT;R26-Tdtomato;Lgr5DTR-eGFP mice were used to ablate the corpus basal Lgr5+ cell population. Constitutional and conditional Wnt5a knockout mice were used to investigate the role of Wnt5a in wound repair and lineage tracing from the Mist1+ stem cells. In both models of gastric injury, Mist1+ isthmus stem cells more rapidly proliferate and trace entire gastric glands compared to the normal state. In regenerating tissue, the number of traced gastric chief cells was significantly reduced, and ablation of Lgr5+ chief cells did not affect Mist1-derived lineage tracing and tissue regeneration. Genetic deletion of Wnt5a impaired proliferation in the gastric isthmus and lineage tracing from Mist1+ stem cells. Similarly, depletion of innate lymphoid cells (ILC2), the main source of Wnt5a, also resulted in reduced proliferation and Mist1+ isthmus cell tracing. Gastric Mist1+ isthmus cells are the main supplier of regenerated glands and are activated in part through Wnt5a pathway.
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影响因子：
24.5
作者：
Hayakawa Y;Jin G;Wang H;Chen X;Westphalen CB;Asfaha S;Renz BW;Ariyama H;Dubeykovskaya ZA;Takemoto Y;Lee Y;Muley A;Tailor Y;Chen D;Muthupalani S;Fox JG;Shulkes A;Worthley DL;Takaishi S;Wang TC
通讯作者：
Wang TC
影响因子：
29.4
作者：
Mills JC;Shivdasani RA
通讯作者：
Shivdasani RA
DOI：
10.1002/stem.2691
发表时间：
2017-11
期刊：
Stem cells (Dayton, Ohio)
影响因子：
--
作者：
Dickinson SC;Sutton CA;Brady K;Salerno A;Katopodi T;Williams RL;West CC;Evseenko D;Wu L;Pang S;Ferro de Godoy R;Goodship AE;Péault B;Blom AW;Kafienah W;Hollander AP
通讯作者：
Hollander AP
影响因子：
29.4
作者：
Hata M;Kinoshita H;Hayakawa Y;Konishi M;Tsuboi M;Oya Y;Kurokawa K;Hayata Y;Nakagawa H;Tateishi K;Fujiwara H;Hirata Y;Worthley DL;Muranishi Y;Furukawa T;Kon S;Tomita H;Wang TC;Koike K
通讯作者：
Koike K
影响因子：
8
作者：
Linke, F.;Zaunig, S.;Kube, D.
通讯作者：
Kube, D.