Prmt5 is essential for intestinal stem cell maintenance and homeostasis
Abstract Intestinal homeostasis relies on the continuous renewal of intestinal stem cells (ISCs), which could be epigenetically regulated. While protein arginine methyltransferase 5 (Prmt5) is known to play a key role in multiple organs as an epigenetic modifier, its specific function in maintaining...
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| Format: | Article |
| Language: | English |
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SpringerOpen
2025-02-01
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| Series: | Cell Regeneration |
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| Online Access: | https://doi.org/10.1186/s13619-024-00216-8 |
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| author | Li Yang Xuewen Li Chenyi Shi Bing Zhao |
| author_facet | Li Yang Xuewen Li Chenyi Shi Bing Zhao |
| author_sort | Li Yang |
| collection | DOAJ |
| description | Abstract Intestinal homeostasis relies on the continuous renewal of intestinal stem cells (ISCs), which could be epigenetically regulated. While protein arginine methyltransferase 5 (Prmt5) is known to play a key role in multiple organs as an epigenetic modifier, its specific function in maintaining intestinal homeostasis remains to be elucidated. Here, we show that Prmt5 is highly expressed in mouse crypts. The deletion of Prmt5 results in ISCs deficiency, ectopic localization of Paneth cells, and spontaneous colitis. Mechanistically, Prmt5 sustains a high level of H3K27ac accumulation by inhibiting Hdac9 expression in the intestinal epithelium, and maintains the stemness of ISCs in a cell-autonomous manner. Notably, inhibition of histone deacetylases can rescue both self‐renewal and differentiation capacities of Prmt5‐depleted ISCs. These findings highlight Prmt5 as a critical regulator in intestinal epithelium development and tissue homeostasis. |
| format | Article |
| id | doaj-art-841da99637f442ad8680e6c321628e27 |
| institution | Kabale University |
| issn | 2045-9769 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | SpringerOpen |
| record_format | Article |
| series | Cell Regeneration |
| spelling | doaj-art-841da99637f442ad8680e6c321628e272025-02-09T12:39:59ZengSpringerOpenCell Regeneration2045-97692025-02-0114111410.1186/s13619-024-00216-8Prmt5 is essential for intestinal stem cell maintenance and homeostasisLi Yang0Xuewen Li1Chenyi Shi2Bing Zhao3State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan UniversityState Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan UniversityState Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan UniversitySchool of Basic Medical Sciences, Jiangxi Medical College, The First Affiliated Hospital of Nanchang University, Nanchang UniversityAbstract Intestinal homeostasis relies on the continuous renewal of intestinal stem cells (ISCs), which could be epigenetically regulated. While protein arginine methyltransferase 5 (Prmt5) is known to play a key role in multiple organs as an epigenetic modifier, its specific function in maintaining intestinal homeostasis remains to be elucidated. Here, we show that Prmt5 is highly expressed in mouse crypts. The deletion of Prmt5 results in ISCs deficiency, ectopic localization of Paneth cells, and spontaneous colitis. Mechanistically, Prmt5 sustains a high level of H3K27ac accumulation by inhibiting Hdac9 expression in the intestinal epithelium, and maintains the stemness of ISCs in a cell-autonomous manner. Notably, inhibition of histone deacetylases can rescue both self‐renewal and differentiation capacities of Prmt5‐depleted ISCs. These findings highlight Prmt5 as a critical regulator in intestinal epithelium development and tissue homeostasis.https://doi.org/10.1186/s13619-024-00216-8Prmt5Intestinal stem cellsHomeostasisH3K27ac |
| spellingShingle | Li Yang Xuewen Li Chenyi Shi Bing Zhao Prmt5 is essential for intestinal stem cell maintenance and homeostasis Cell Regeneration Prmt5 Intestinal stem cells Homeostasis H3K27ac |
| title | Prmt5 is essential for intestinal stem cell maintenance and homeostasis |
| title_full | Prmt5 is essential for intestinal stem cell maintenance and homeostasis |
| title_fullStr | Prmt5 is essential for intestinal stem cell maintenance and homeostasis |
| title_full_unstemmed | Prmt5 is essential for intestinal stem cell maintenance and homeostasis |
| title_short | Prmt5 is essential for intestinal stem cell maintenance and homeostasis |
| title_sort | prmt5 is essential for intestinal stem cell maintenance and homeostasis |
| topic | Prmt5 Intestinal stem cells Homeostasis H3K27ac |
| url | https://doi.org/10.1186/s13619-024-00216-8 |
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