Lymphangiocrine signals are required for proper intestinal repair after cytotoxic injury.
Lymphangiocrine signals are required for proper intestinal repair after cytotoxic injury.
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淋巴管分泌信号是细胞毒性损伤后肠修复所必需的。
DOI：
10.1016/j.stem.2022.07.007
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发表时间：
2022-08-04
期刊：
影响因子：
23.9
通讯作者：
Klein, Ophir
中科院分区：
文献类型：
--
作者：
Palikuqi, Brisa;Rispal, Jeremie;Reyes, Efren A.;Vaka, Dedeepya;Boffelli, Dario;Klein, Ophir
肠上皮细胞经历持续的更新，并在损伤后具有特殊的再生能力。肠道干细胞（ISCs）的维持和增殖受其周围生态位的调节，主要通过Wnt信号传导。然而，目前还不清楚哪些小生境细胞在不同的损伤状态下产生信号，内皮细胞（EC）作为ISC小生境的组成部分在稳态和损伤后的作用一直未得到充分重视。在这里，我们表明，淋巴管内皮细胞（LEC）居住在接近隐窝上皮细胞和分泌分子，支持上皮更新和修复。LEC是小肠中Wnt信号传导的重要来源，因为LEC衍生的Rspo3的损失导致干细胞和祖细胞数量减少，并阻碍细胞毒性损伤后的恢复。总之，我们的研究结果将LEC确定为细胞毒性损伤后最佳肠道恢复的重要生态位成分。Palikuqi等人采用透明肠组织成像、转录分析和遗传小鼠模型来研究淋巴管内皮细胞在肠干细胞生态位中的作用。作者证明，淋巴管内皮细胞是细胞毒性损伤后适当肠道恢复的Rspo 3的重要来源。
The intestinal epithelium undergoes continuous renewal and has an exceptional capacity to regenerate after injury. Maintenance and proliferation of intestinal stem cells (ISCs) are regulated by their surrounding niche, largely through Wnt signaling. However, it remains unclear which niche cells produce signals during different injury states, and the role of endothelial cells (ECs) as a component of the ISC niche during homeostasis and after injury has been underappreciated. Here, we show that lymphatic endothelial cells (LECs) reside in proximity to crypt epithelial cells and secrete molecules that support epithelial renewal and repair. LECs are an essential source of Wnt signaling in the small intestine, as loss of LEC-derived Rspo3 leads to a lower number of stem and progenitor cells and hinders recovery after cytotoxic injury. Together, our findings identify LECs as an essential niche component for optimal intestinal recovery after cytotoxic injury. Palikuqi et al. employ imaging of cleared intestinal tissue, transcriptional analyses and genetic mouse models to investigate the role of lymphatic endothelial cells in the intestinal stem cell niche. The authors demonstrate that lymphatic endothelial cells are an essential source of Rspo3 for proper intestinal recovery after cytotoxic injury.
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影响因子：
23.9
作者：
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Rafii S
影响因子：
23.9
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Yilmaz, Omer H.
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通讯作者：
Simmons A
影响因子：
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作者：
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通讯作者：
Cong, Feng
影响因子：
3.1
作者：
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通讯作者：
Lange, S