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2篇 您的检索式:作者名="Tiankun Lu"
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1Gut microbiota drives macrophage-dependent self-renewal of intestinal stem cells via niche enteric serotonergic neurons显示文摘Lgr5+intestinal stem cells(ISCs)reside within specialized niches at the crypt base and harbor self-renewal and differentiation capacities.ISCs in the crypt base are sustained by their surrounding niche for precise modulation of self-renewal and differentiation.However,how intestinal cells in the crypt niche and microbiota in enteric cavity coordinately regulate ISC stemness remains unclear.Here,we show that ISCs are regulated by microbiota and niche enteric serotonergic neurons.The gut microbiota metabolite valeric acid promotes Tph2 expression in enteric serotonergic neurons via blocking the recruitment of the NuRD complex onto Tph2 promoter.5-hydroxytryptamine(5-HT)in turn activates PGE2 production in a PGE2+macrophage subset through its receptors HTR2A/3 A;and PGE2 via binding its receptors EP1/EP4,promotes Wnt/β-catenin signaling in ISCs to promote their self-renewal.Our findings illustrate a complex crosstalk among microbiota,intestinal nerve cells,intestinal immune cells and ISCs,revealing a new layer of ISC regulation by niche cells and microbiota.Pingping Zhu Tiankun Lu Jiayi Wu Dongdong Fan Benyu Liu Xiaoxiao Zhu Hui Guo Ying Du Feng Liu Yong Tian Zusen Fan 2022Cell Research2022,32,6:8
2Circular RNA circZbtb20 maintains ILC3 homeostasis and function via Alkbh5-dependent m6A demethylation of Nr4a1 mRNA显示文摘Group 3 innate lymphoid cells(ILC3s)play critical roles in innate immunity and gut homeostasis.However,how ILC3 homeostasis is regulated remains elusive.Here,we identified a novel circular RNA,circZbtb20,that is highly expressed in ILC3s and required for their maintenance and function.CircZbtb20 deletion causes reduced ILC3 numbers,increasing susceptibility to C.rodentium infection.Mechanistically,circZbtb20 enhances the interaction of Alkbh5 with Nr4a1 mRNA,leading to ablation of the m6A modification of Nr4a1 mRNA to promote its stability.Nr4a1 initiates Notch2 signaling activation,which contributes to the maintenance of ILC3 homeostasis.Deletion of Alkbh5 or Nr4a1 also impairs ILC3 homeostasis and increases susceptibilities to bacterial infection.Thus,our findings reveal an important role of circular RNA in the regulation of innate lymphoid cell homeostasis.Benyu Liu Nian Liu Xiaoxiao Zhu Liuliu Yang Buqing Ye Huimu Li Pingping Zhu Tiankun Lu Yong Tian Zusen Fan 2021Cellular & Molecular Immunology2021,18,6:2
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