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IFT140/K14 细胞在唾液腺中作为干细胞/祖细胞发挥作用。

IFT140/K14 cells function as stem/progenitor cells in salivary glands.

机构信息

Department of Oral and Maxillofacial Surgery, Stomatological Hospital and Dental School of Tongji University, Shanghai Engineering Research Center of Tooth Restoration and Regeneration, No. 399, YanChang Middle Road, Shanghai, China.

Department of Implantology, Stomatological Hospital and Dental School of Tongji University, Shanghai Engineering Research Center of Tooth Restoration and Regeneration, No. 399, YanChang Middle Road, Shanghai, China.

出版信息

Int J Oral Sci. 2022 Oct 10;14(1):49. doi: 10.1038/s41368-022-00200-5.

DOI:10.1038/s41368-022-00200-5
PMID:36216809
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9550827/
Abstract

Stem/progenitor cells are important for salivary gland development, homeostasis maintenance, and regeneration following injury. Keratin-14 (K14) cells have been recognized as bona fide salivary gland stem/progenitor cells. However, K14 is also expressed in terminally differentiated myoepithelial cells; therefore, more accurate molecular markers for identifying salivary stem/progenitor cells are required. The intraflagellar transport (IFT) protein IFT140 is a core component of the IFT system that functions in signaling transduction through the primary cilia. It is reportedly expressed in mesenchymal stem cells and plays a role in bone formation. In this study, we demonstrated that IFT140 was intensively expressed in K14 stem/progenitor cells during the developmental period and early regeneration stage following ligation-induced injuries in murine submandibular glands. In addition, we demonstrated that IFT140/ K14 could self-renew and differentiate into granular duct cells at the developmental stage in vivo. The conditional deletion of Ift140 from K14 cells caused abnormal epithelial structure and function during salivary gland development and inhibited regeneration. IFT140 partly coordinated the function of K14 stem/progenitor cells by modulating ciliary membrane trafficking. Our investigation identified a combined marker, IFT140/K14, for salivary gland stem/progenitor cells and elucidated the essential role of IFT140 and cilia in regulating salivary stem/progenitor cell differentiation and gland regeneration.

摘要

干细胞/祖细胞对于唾液腺的发育、稳态维持以及损伤后的再生至关重要。角蛋白 14（K14）细胞已被认为是真正的唾液腺干细胞/祖细胞。然而，K14 也在终末分化的肌上皮细胞中表达；因此，需要更准确的分子标志物来识别唾液干细胞/祖细胞。纤毛内运输（IFT）蛋白 IFT140 是 IFT 系统的核心组成部分，在初级纤毛中的信号转导中发挥作用。据报道，它在间充质干细胞中表达，并在骨形成中发挥作用。在这项研究中，我们证明了在结扎诱导的小鼠下颌下腺损伤后的发育期间和早期再生阶段，IFT140 在 K14 干细胞/祖细胞中强烈表达。此外，我们证明了 IFT140/K14 可以在体内发育阶段自我更新并分化为颗粒导管细胞。从 K14 细胞中条件性缺失 Ift140 会导致唾液腺发育过程中上皮结构和功能异常，并抑制再生。IFT140 通过调节纤毛膜运输部分协调 K14 干细胞/祖细胞的功能。我们的研究确定了一个联合标志物，IFT140/K14，用于唾液腺干细胞/祖细胞，并阐明了 IFT140 和纤毛在调节唾液干细胞/祖细胞分化和腺体再生中的重要作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/57f3/9550827/3aef0ca75351/41368_2022_200_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/57f3/9550827/6183600b44ad/41368_2022_200_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/57f3/9550827/a65f12a35c4f/41368_2022_200_Fig2_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/57f3/9550827/a3a002a893c0/41368_2022_200_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/57f3/9550827/08b91066f877/41368_2022_200_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/57f3/9550827/7ed666ca8576/41368_2022_200_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/57f3/9550827/91ff52bf4e27/41368_2022_200_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/57f3/9550827/3aef0ca75351/41368_2022_200_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/57f3/9550827/6183600b44ad/41368_2022_200_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/57f3/9550827/a65f12a35c4f/41368_2022_200_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/57f3/9550827/aed2f2b3c54f/41368_2022_200_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/57f3/9550827/a3a002a893c0/41368_2022_200_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/57f3/9550827/08b91066f877/41368_2022_200_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/57f3/9550827/7ed666ca8576/41368_2022_200_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/57f3/9550827/91ff52bf4e27/41368_2022_200_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/57f3/9550827/3aef0ca75351/41368_2022_200_Fig8_HTML.jpg

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The structural basis of intraflagellar transport at a glance.鞭毛内运输的结构基础一览。
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