Expression of Piwi protein MIWI2 defines a distinct population of multiciliated cells.
Expression of Piwi protein MIWI2 defines a distinct population of multiciliated cells.
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Piwi 蛋白 MIWI2 的表达定义了一个独特的多纤毛细胞群。
DOI：
10.1172/jci94639
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发表时间：
2017
期刊：
影响因子：
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通讯作者：
Mizgerd,JosephP
中科院分区：
文献类型：
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作者：
Wasserman,GregoryA;Szymaniak,AleksanderD;Hinds,AnneC;Yamamoto,Kazuko;Kamata,Hirofumi;Smith,NicoleMs;Hilliard,KristieL;Carrieri,Claudia;Labadorf,AdamT;Quinton,LeeJ;Ai,Xingbin;Varelas,Xaralabos;Chen,Felicia;Mizgerd,JosephP
P 元素诱导的弱睾丸 (Piwi) 蛋白因抑制哺乳动物种系中逆转录转座子的激活而闻名。然而，Piwi 蛋白或 Piwi 依赖性功能是否发生在哺乳动物体细胞中尚不清楚。与种系限制性表达相反，我们观察到 Piwi-likeMiwi2mRNA 确实在成年小鼠的肺上皮细胞中表达，并且在肺炎期间被诱导表达。进一步的研究表明，MIWI2 蛋白定位于离散的多纤毛气道上皮细胞群的细胞质。 MIWI2 阳性多纤毛细胞的分离和下一代测序表明，它们在表型上与邻近的 MIWI2 阴性多纤毛细胞不同。缺乏 MIWI2 的小鼠表现出气道上皮细胞平衡的改变，表现为多纤毛细胞减少和球杆细胞增加。在肺炎球菌肺炎期间，Miwi2 缺陷小鼠表现出炎症介质表达增加和免疫细胞募集增加，从而导致细菌清除增强。总而言之，我们的数据描绘了种系之外的 MIWI2 依赖性功能，并证明了气道多纤毛细胞的不同亚群的存在，这些细胞可以通过 MIWI2 表达来区分。通过证明 MIWI2 在气道细胞识别和肺部先天免疫中的作用，这些研究阐明了 Piwi 蛋白在体组织中意想不到的生理功能。
P-element–induced wimpy testes (Piwi) proteins are known for suppressing retrotransposon activation in the mammalian germline. However, whether Piwi protein or Piwi-dependent functions occur in the mammalian soma is unclear. Contrary to germline-restricted expression, we observed that Piwi-likeMiwi2mRNA is indeed expressed in epithelial cells of the lung in adult mice and that it is induced during pneumonia. Further investigation revealed that MIWI2 protein localized to the cytoplasm of a discrete population of multiciliated airway epithelial cells. Isolation and next-generation sequencing of MIWI2-positive multiciliated cells revealed that they are phenotypically distinct from neighboring MIWI2-negative multiciliated cells. Mice lacking MIWI2 exhibited an altered balance of airway epithelial cells, demonstrating fewer multiciliated cells and an increase in club cells. During pneumococcal pneumonia,Miwi2-deficient mice exhibited increased expression of inflammatory mediators and increased immune cell recruitment, leading to enhanced bacterial clearance. Taken together, our data delineate MIWI2-dependent functions outside of the germline and demonstrate the presence of distinct subsets of airway multiciliated cells that can be discriminated by MIWI2 expression. By demonstrating roles for MIWI2 in airway cell identity and pulmonary innate immunity, these studies elucidate unanticipated physiological functions for Piwi proteins in somatic tissues.