Mouse Intestinal Krt15+ Crypt Cells Are Radio-Resistant and Tumor Initiating.
Mouse Intestinal Krt15+ Crypt Cells Are Radio-Resistant and Tumor Initiating.
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DOI：
10.1016/j.stemcr.2018.04.022
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发表时间：
2018-06-05
影响因子：
5.9
通讯作者：
Rustgi AK
中科院分区：
文献类型：
--
作者：
Giroux V;Stephan J;Chatterji P;Rhoades B;Wileyto EP;Klein-Szanto AJ;Lengner CJ;Hamilton KE;Rustgi AK
两个主要的干细胞池协调肠上皮细胞的快速更新。快速循环的 Lgr5+ 干细胞插入隐窝基底 (CBC) 的潘氏细胞之间，而抗损伤储备干细胞则位于隐窝基底上方。中间丝角蛋白 15 (Krt15) 标记干细胞或长寿祖细胞，有助于毛囊或食道上皮的组织修复。在此，我们证明 Krt15 通过谱系追踪标记小肠隐窝中的长寿和多能细胞。 Krt15+ 隐窝细胞在体内和 3D 类器官培养中表现出自我更新潜力。 Krt15+ 隐窝细胞能够抵抗高剂量辐射，并有助于损伤后的上皮再生。值得注意的是，Krt15+ 细胞中肿瘤抑制因子 Apc 的缺失会导致腺瘤和腺癌的形成。这些结果表明，Krt15 标记了长寿、多能和抗损伤的隐窝细胞，这些细胞可能作为肠癌的起源细胞。 Krt15 标记小鼠小肠中的多能和自我更新的隐窝细胞 Krt15+ 隐窝细胞具有放射抗性，有助于损伤后的再生 Krt15+ 细胞中 Apc 的丢失导致肠腺瘤和腺癌的形成 Krt15+ 细胞可能作为肠癌的起源细胞。在这篇文章中，Rustgi 及其同事鉴定了肠隐窝内的一个新的长寿细胞群，以 Krt15 启动子为标志。 Krt15+ 细胞是自我更新、多能且抗辐射的细胞，有助于从辐射引起的损伤中恢复。此外，这些细胞当以 Apc 损失为目标时，会转化为腺瘤和腺癌。
Two principal stem cell pools orchestrate the rapid cell turnover in the intestinal epithelium. Rapidly cycling Lgr5+ stem cells are intercalated between the Paneth cells at the crypt base (CBCs) and injury-resistant reserve stem cells reside above the crypt base. The intermediate filament Keratin 15 (Krt15) marks either stem cells or long-lived progenitor cells that contribute to tissue repair in the hair follicle or the esophageal epithelium. Herein, we demonstrate that Krt15 labels long-lived and multipotent cells in the small intestinal crypt by lineage tracing. Krt15+ crypt cells display self-renewal potential in vivo and in 3D organoid cultures. Krt15+ crypt cells are resistant to high-dose radiation and contribute to epithelial regeneration following injury. Notably, loss of the tumor suppressor Apc in Krt15+ cells leads to adenoma and adenocarcinoma formation. These results indicate that Krt15 marks long-lived, multipotent, and injury-resistant crypt cells that may function as a cell of origin in intestinal cancer. Krt15 marks multipotent and self-renewing crypt cells in the mouse small intestine Krt15+ crypt cells are radio-resistant and contribute to regeneration following injury Apc loss in Krt15+ cells leads to intestinal adenoma and adenocarcinoma formation Krt15+ cells may function as a cell of origin in intestinal cancer In this article, Rustgi and colleagues identify a new population of long-lived cells within the intestinal crypt, marked by the Krt15 promoter. Krt15+ cells are self-renewing, multipotent, and radio-resistant cells that facilitate recovery from radiation-induced injury. Furthermore, such cells, when targeted with Apc loss, undergo transformation to adenomas and adenocarcinomas.
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影响因子：
23.9
作者：
Jadhav U;Saxena M;O'Neill NK;Saadatpour A;Yuan GC;Herbert Z;Murata K;Shivdasani RA
通讯作者：
Shivdasani RA
影响因子：
4.5
作者：
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影响因子：
46.9
作者：
Morris, RJ;Liu, YP;Cotsarelis, G
通讯作者：
Cotsarelis, G
影响因子：
64.8
作者：
Buczacki, Simon J. A.;Zecchini, Heather Ireland;Winton, Douglas J.
通讯作者：
Winton, Douglas J.
影响因子：
64.8
作者：
Kim, S;Wong, P;Coulombe, PA
通讯作者：
Coulombe, PA