Notch1 and Notch2 receptors regulate mouse and human gastric antral epithelial cell homoeostasis.
Notch1 and Notch2 receptors regulate mouse and human gastric antral epithelial cell homoeostasis.
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DOI：
10.1136/gutjnl-2015-310811
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发表时间：
2017-06
期刊：
影响因子：
24.5
通讯作者：
Samuelson LC
中科院分区：
文献类型：
--
作者：
Gifford GB;Demitrack ES;Keeley TM;Tam A;La Cunza N;Dedhia PH;Spence JR;Simeone DM;Saotome I;Louvi A;Siebel CW;Samuelson LC
我们测试了 Notch 通路受体 Notch1 和 Notch2 调节小鼠和人胃窦组织干细胞和上皮细胞稳态的能力。小鼠接受泛 Notch 抑制剂二苯并氮卓 (DBZ) 或针对 Notch1 和/或 Notch2 的抑制性抗体治疗。通过组织学和分子方法测量上皮增殖、凋亡和细胞分化。从小鼠和人类的窦腺中建立了类器官；用Notch抑制剂处理后测量生长和分化。 Notch1 和 Notch2 是在小鼠和人类胃窦组织和类器官培养物中表达的主要 Notch 受体。在成年小鼠中联合抑制 Notch1 和 Notch2 会导致上皮细胞增殖减少，包括 LGR5 干细胞增殖减少和细胞凋亡增加，与 DBZ 整体 Notch 抑制的反应类似。抑制个别受体后观察到不太明显的效果。 DBZ 抑制 Notch 通路或联合抑制 Notch1 和 Notch2 会导致所有胃窦谱系的分化增加，并重塑细胞以表达通常与胃肠道其他区域（包括肠道）相关的分泌产物。对小鼠和人类类器官的分析表明，通过 Notch1 和 Notch2 的 Notch 信号传导是上皮细胞固有的，并且是类器官生长所必需的。 Notch信号传导是维持胃窦干细胞所必需的。 Notch1 和 Notch2 是调节小鼠和人胃上皮细胞稳态的主要 Notch 受体。
We tested the ability of Notch pathway receptors Notch1 and Notch2 to regulate stem and epithelial cell homoeostasis in mouse and human gastric antral tissue. Mice were treated with the pan-Notch inhibitor dibenzazepine (DBZ) or inhibitory antibodies targeting Notch1 and/or Notch2. Epithelial proliferation, apoptosis and cellular differentiation were measured by histological and molecular approaches. Organoids were established from mouse and human antral glands; growth and differentiation were measured after treatment with Notch inhibitors. Notch1 and Notch2 are the predominant Notch receptors expressed in mouse and human antral tissue and organoid cultures. Combined inhibition of Notch1 and Notch2 in adult mice led to decreased epithelial cell proliferation, including reduced proliferation of LGR5 stem cells, and increased apoptosis, similar to the response to global Notch inhibition with DBZ. Less pronounced effects were observed after inhibition of individual receptors. Notch pathway inhibition with DBZ or combined inhibition of Notch1 and Notch2 led to increased differentiation of all gastric antral lineages, with remodelling of cells to express secretory products normally associated with other regions of the GI tract, including intestine. Analysis of mouse and human organoids showed that Notch signalling through Notch1 and Notch2 is intrinsic to the epithelium and required for organoid growth. Notch signalling is required to maintain gastric antral stem cells. Notch1 and Notch2 are the primary Notch receptors regulating epithelial cell homoeostasis in mouse and human stomach.
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影响因子：
24.5
作者：
VanDussen KL;Marinshaw JM;Shaikh N;Miyoshi H;Moon C;Tarr PI;Ciorba MA;Stappenbeck TS
通讯作者：
Stappenbeck TS
DOI：
10.1152/ajpgi.00461.2005
发表时间：
2006-05-01
影响因子：
4.5
作者：
Lopez-Diaz, L;Hinkle, KL;Samuelson, LC
通讯作者：
Samuelson, LC
影响因子：
64.8
作者：
van Es, JH;van Gijn, ME;Clevers, H
通讯作者：
Clevers, H
影响因子：
4.6
作者：
VanDussen, Kelli L.;Carulli, Alexis J.;Samuelson, Linda C.
通讯作者：
Samuelson, Linda C.
影响因子：
64.8
作者：
Wu, Yan;Cain-Hom, Carol;Siebel, Christian W.
通讯作者：
Siebel, Christian W.