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Loss of FOXC1 contributes to the corneal epithelial fate switch and pathogenesis
Forkhead box C1 (FOXC1) is required for neural crest and ocular development, and mutations in FOXC1 lead to inherited Axenfeld–Rieger syndrome. Here, we find that FOXC1 and paired box 6 (PAX6) are co-expressed in the human limbus and central corneal epithelium. Deficiency of FOXC1 and alternation in...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7791103/ https://www.ncbi.nlm.nih.gov/pubmed/33414365 http://dx.doi.org/10.1038/s41392-020-00378-2 |
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author | Li, Mingsen Zhu, Liqiong Liu, Jiafeng Huang, Huaxing Guo, Huizhen Wang, Li Li, Lingyu Gu, Sijie Tan, Jieying Zhong, Jing Wang, Bowen Mao, Zhen Fan, Yong Liu, Chunqiao Yuan, Jin Ouyang, Hong |
author_facet | Li, Mingsen Zhu, Liqiong Liu, Jiafeng Huang, Huaxing Guo, Huizhen Wang, Li Li, Lingyu Gu, Sijie Tan, Jieying Zhong, Jing Wang, Bowen Mao, Zhen Fan, Yong Liu, Chunqiao Yuan, Jin Ouyang, Hong |
author_sort | Li, Mingsen |
collection | PubMed |
description | Forkhead box C1 (FOXC1) is required for neural crest and ocular development, and mutations in FOXC1 lead to inherited Axenfeld–Rieger syndrome. Here, we find that FOXC1 and paired box 6 (PAX6) are co-expressed in the human limbus and central corneal epithelium. Deficiency of FOXC1 and alternation in epithelial features occur in patients with corneal ulcers. FOXC1 governs the fate of the corneal epithelium by directly binding to lineage-specific open promoters or enhancers marked by H3K4me2. FOXC1 depletion not only activates the keratinization pathway and reprograms corneal epithelial cells into skin-like epithelial cells, but also disrupts the collagen metabolic process and interferon signaling pathways. Loss of interferon regulatory factor 1 and PAX6 induced by FOXC1 dysfunction is linked to the corneal ulcer. Collectively, our results reveal a FOXC1-mediated regulatory network responsible for corneal epithelial homeostasis and provide a potential therapeutic target for corneal ulcer. |
format | Online Article Text |
id | pubmed-7791103 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-77911032021-01-15 Loss of FOXC1 contributes to the corneal epithelial fate switch and pathogenesis Li, Mingsen Zhu, Liqiong Liu, Jiafeng Huang, Huaxing Guo, Huizhen Wang, Li Li, Lingyu Gu, Sijie Tan, Jieying Zhong, Jing Wang, Bowen Mao, Zhen Fan, Yong Liu, Chunqiao Yuan, Jin Ouyang, Hong Signal Transduct Target Ther Article Forkhead box C1 (FOXC1) is required for neural crest and ocular development, and mutations in FOXC1 lead to inherited Axenfeld–Rieger syndrome. Here, we find that FOXC1 and paired box 6 (PAX6) are co-expressed in the human limbus and central corneal epithelium. Deficiency of FOXC1 and alternation in epithelial features occur in patients with corneal ulcers. FOXC1 governs the fate of the corneal epithelium by directly binding to lineage-specific open promoters or enhancers marked by H3K4me2. FOXC1 depletion not only activates the keratinization pathway and reprograms corneal epithelial cells into skin-like epithelial cells, but also disrupts the collagen metabolic process and interferon signaling pathways. Loss of interferon regulatory factor 1 and PAX6 induced by FOXC1 dysfunction is linked to the corneal ulcer. Collectively, our results reveal a FOXC1-mediated regulatory network responsible for corneal epithelial homeostasis and provide a potential therapeutic target for corneal ulcer. Nature Publishing Group UK 2021-01-08 /pmc/articles/PMC7791103/ /pubmed/33414365 http://dx.doi.org/10.1038/s41392-020-00378-2 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Li, Mingsen Zhu, Liqiong Liu, Jiafeng Huang, Huaxing Guo, Huizhen Wang, Li Li, Lingyu Gu, Sijie Tan, Jieying Zhong, Jing Wang, Bowen Mao, Zhen Fan, Yong Liu, Chunqiao Yuan, Jin Ouyang, Hong Loss of FOXC1 contributes to the corneal epithelial fate switch and pathogenesis |
title | Loss of FOXC1 contributes to the corneal epithelial fate switch and pathogenesis |
title_full | Loss of FOXC1 contributes to the corneal epithelial fate switch and pathogenesis |
title_fullStr | Loss of FOXC1 contributes to the corneal epithelial fate switch and pathogenesis |
title_full_unstemmed | Loss of FOXC1 contributes to the corneal epithelial fate switch and pathogenesis |
title_short | Loss of FOXC1 contributes to the corneal epithelial fate switch and pathogenesis |
title_sort | loss of foxc1 contributes to the corneal epithelial fate switch and pathogenesis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7791103/ https://www.ncbi.nlm.nih.gov/pubmed/33414365 http://dx.doi.org/10.1038/s41392-020-00378-2 |
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