Enteroendocrine and tuft cells support Lgr5 stem cells on Paneth cell depletion
Enteroendocrine and tuft cells support Lgr5 stem cells on Paneth cell depletion
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DOI：
10.1073/pnas.1801888117
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发表时间：
2019-12-26
影响因子：
11.1
通讯作者：
Clevers, Hans
中科院分区：
文献类型：
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作者：
van Es, Johan H.;Wiebrands, Kay;Clevers, Hans
循环肠Lgr5（+）干细胞与其终分化的Paneth子细胞在隐窝底部混在一起。Paneth细胞提供多种分泌的（如Wnt， EGF）以及表面结合的（Notch配体）生态位信号。本研究表明，使用插入p溶菌酶位点的白喉毒素受体基因消融小鼠Paneth细胞不会影响Lgr5（+）干细胞的维持。流式细胞术、单细胞测序和组织学分析显示，消融的Paneth细胞被肠内分泌细胞和簇状细胞所取代。由于这些细胞占据了Lgr5（+）干细胞之间的Paneth细胞位置，它们作为Notch信号的替代来源，而Notch信号对于Lgr5（+）干细胞的维持至关重要。我们的综合体内结果强调了肠道在维持正常组织稳态方面的适应性灵活性。
Cycling intestinal Lgr5(+) stem cells are intermingled with their terminally differentiated Paneth cell daughters at crypt bottoms. Paneth cells provide multiple secreted (e.g., Wnt, EGF) as well as surface-bound (Notch ligand) niche signals. Here we show that ablation of Paneth cells in mice, using a diphtheria toxin receptor gene inserted into the P-lysozyme locus, does not affect the maintenance of Lgr5(+) stem cells. Flow cytometry, single-cell sequencing, and histological analysis showed that the ablated Paneth cells are replaced by enteroendocrine and tuft cells. As these cells physically occupy Paneth cell positions between Lgr5(+) stem cells, they serve as an alternative source of Notch signals, which are essential for Lgr5(+) stem cell maintenance. Our combined in vivo results underscore the adaptive flexibility of the intestine in maintaining normal tissue homeostasis.