Lymphatics and fibroblasts support intestinal stem cells in homeostasis and injury.
Lymphatics and fibroblasts support intestinal stem cells in homeostasis and injury.
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淋巴管和成纤维细胞在稳态和损伤状态下支持肠道干细胞。
DOI：
10.1016/j.stem.2022.06.013
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发表时间：
2022-08-04
期刊：
影响因子：
23.9
通讯作者：
Yilmaz, Omer H.
中科院分区：
文献类型：
--
作者：
Goto, Norihiro;Goto, Saori;Imada, Shinya;Hosseini, Sahar;Deshpande, Vikram;Yilmaz, Omer H.
Lgr 5+肠干细胞（ISCs）依赖于其适当功能的生态位因子。然而，这些ISC生态位因子的来源以及它们如何在体内支持ISC仍然存在争议。在这里，我们报告说，ISCs依赖于淋巴管内皮细胞（LEC）和RSPO 3 + GREM 1+成纤维细胞（RGFs）。在肠和结肠中，LEC被RGF包围并且位于隐窝基部的ISC附近。LEC和RGFs都提供了关键的ISC生态位因子RSPO 3来支持ISC，其中两种细胞类型中的RSPO 3损失极大地损害了ISC数量、绒毛长度和损伤后的修复。在对损伤的反应中，LEC和RGF数量增加并产生更大量的RSPO 3和其他生长/血管分泌因子以促进肠道修复。我们建议，LEC代表了一种新的利基组成部分的ISCs，它与RGFs一起，作为主要的体内RSPO 3来源的ISCs的稳态和损伤介导的再生。后藤及其同事将淋巴管内皮细胞（LEC）和RSPO 3 + GREM 1+成纤维细胞（RGFs）鉴定为肠干细胞（ISC）的基质生态位组分。LEC和RGF通过产生RSPO 3和GREM 1维持ISC的稳态。在损伤中，LECS和RGFs数量增加并产生生长/淋巴管分泌因子以协调ISC介导的修复。
Lgr5+ intestinal stem cells (ISCs) depend on niche factors for their proper function. However, the source of these ISC niche factors and how they support ISCs in vivo remain controversial. Here, we report that ISCs depend on lymphatic endothelial cells (LECs) and RSPO3+GREM1+ fibroblasts (RGFs). In the intestine and colon, LECs are surrounded by RGFs and are located near ISCs at the crypt base. Both LECs and RGFs provide the critical ISC niche factor RSPO3 to support ISCs, where RSPO3 loss in both cell types drastically compromises ISC numbers, villi length, and repair after injury. In response to injury, LEC and RGF numbers expand and produce greater amounts of RSPO3 and other growth/angiocrine factors to foster intestinal repair. We propose that LECs represent a novel niche component for ISCs, which together with RGFs, serve as the major in vivo RSPO3 source for ISCs in homeostasis and injury-mediated regeneration. Goto and colleagues identify lymphatic endothelial cells (LECs) and RSPO3+GREM1+ fibroblasts (RGFs) as stromal niche components of intestinal stem cells (ISCs). LECs and RGFs sustain ISCs through the production RSPO3 and GREM1 in homeostasis. In injury, LECS and RGFs expand in number and produce growth/lymphangiocrine factors to orchestrate ISC-mediated repair.
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影响因子：
10.5
作者：
de Lau W;Peng WC;Gros P;Clevers H
通讯作者：
Clevers H
影响因子：
64.5
作者：
Kinchen J;Chen HH;Parikh K;Antanaviciute A;Jagielowicz M;Fawkner-Corbett D;Ashley N;Cubitt L;Mellado-Gomez E;Attar M;Sharma E;Wills Q;Bowden R;Richter FC;Ahern D;Puri KD;Henault J;Gervais F;Koohy H;Simmons A
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Simmons A
影响因子：
4.6
作者：
Karaman, Sinem;Leppanen, Veli-Matti;Alitalo, Kari
通讯作者：
Alitalo, Kari
影响因子：
29.4
作者：
Farin, Henner F.;Van Es, Johan H.;Clevers, Hans
通讯作者：
Clevers, Hans
DOI：
10.1073/pnas.1713510115
发表时间：
2018-04-03
影响因子：
11.1
作者：
Greicius G;Kabiri Z;Sigmundsson K;Liang C;Bunte R;Singh MK;Virshup DM
通讯作者：
Virshup DM