Mist1 Expressing Gastric Stem Cells Maintain the Normal and Neoplastic Gastric Epithelium and Are Supported by a Perivascular Stem Cell Niche.
Mist1 Expressing Gastric Stem Cells Maintain the Normal and Neoplastic Gastric Epithelium and Are Supported by a Perivascular Stem Cell Niche.
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DOI：
10.1016/j.ccell.2015.10.003
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发表时间：
2015-12-14
期刊：
影响因子：
50.3
通讯作者：
Wang TC
中科院分区：
文献类型：
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作者：
Hayakawa Y;Ariyama H;Stancikova J;Sakitani K;Asfaha S;Renz BW;Dubeykovskaya ZA;Shibata W;Wang H;Westphalen CB;Chen X;Takemoto Y;Kim W;Khurana SS;Tailor Y;Nagar K;Tomita H;Hara A;Sepulveda AR;Setlik W;Gershon MD;Saha S;Ding L;Shen Z;Fox JG;Friedman RA;Konieczny SF;Worthley DL;Korinek V;Wang TC
正常胃腺和肿瘤胃腺的调节和干细胞来源尚不确定。在这里，我们发现Mist1的表达标志着胃体峡部静止的干细胞。Mist1+干细胞是Kras和APC突变相结合的肠型癌和E-钙粘素缺失的弥漫型癌的起源细胞。弥漫型肿瘤的发生依赖于由CXCL12+的内皮细胞和CXCR4+的胃固有淋巴样细胞(ILCs)介导的炎症。这些细胞形成血管周围的胃干细胞生态位，ILCs产生的Wnt5a激活RhoA以抑制E-钙粘素缺失细胞中的失巢凋亡。靶向CXCR4、ILCs或Wnt5a可抑制弥漫型胃癌的发生，为肿瘤胃干细胞定位提供靶点。
The regulation and stem cell origin of normal and neoplastic gastric glands are uncertain. Here, we show that Mist1 expression marks quiescent stem cells in the gastric corpus isthmus. Mist1+ stem cells serve as a cell-of-origin for intestinal-type cancer with the combination of Kras and Apc mutation, and for diffuse-type cancer with the loss of E-cadherin. Diffuse-type cancer development is dependent on inflammation mediated by Cxcl12+ endothelial cells and Cxcr4+ gastric innate lymphoid cells (ILCs). These cells form the perivascular gastric stem cell niche, and Wnt5a produced from ILCs activates RhoA to inhibit anoikis in the E-cadherin-depleted cells. Targeting Cxcr4, ILCs, or Wnt5a inhibits diffuse-type gastric carcinogenesis, providing targets within the neoplastic gastric stem cell niche.