NUP62 alleviates senescence and promotes the stemness of human dental pulp stem cells via NSD2-dependent epigenetic reprogramming
Abstract Stem cells play a crucial role in maintaining tissue regenerative capacity and homeostasis. However, mechanisms associated with stem cell senescence require further investigation. In this study, we conducted a proteomic analysis of human dental pulp stem cells (HDPSCs) obtained from individ...
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2025-04-01
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| Series: | International Journal of Oral Science |
| Online Access: | https://doi.org/10.1038/s41368-025-00362-y |
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| author | Xiping Wang Li Wang Linxi Zhou Lu Chen Jiayi Shi Jing Ge Sha Tian Zihan Yang Yuqiong Zhou Qihao Yu Jiacheng Jin Chen Ding Yihuai Pan Duohong Zou |
| author_facet | Xiping Wang Li Wang Linxi Zhou Lu Chen Jiayi Shi Jing Ge Sha Tian Zihan Yang Yuqiong Zhou Qihao Yu Jiacheng Jin Chen Ding Yihuai Pan Duohong Zou |
| author_sort | Xiping Wang |
| collection | DOAJ |
| description | Abstract Stem cells play a crucial role in maintaining tissue regenerative capacity and homeostasis. However, mechanisms associated with stem cell senescence require further investigation. In this study, we conducted a proteomic analysis of human dental pulp stem cells (HDPSCs) obtained from individuals of various ages. Our findings showed that the expression of NUP62 was decreased in aged HDPSCs. We discovered that NUP62 alleviated senescence-associated phenotypes and enhanced differentiation potential both in vitro and in vivo. Conversely, the knocking down of NUP62 expression aggravated the senescence-associated phenotypes and impaired the proliferation and migration capacity of HDPSCs. Through RNA-sequence and decoding the epigenomic landscapes remodeled induced by NUP62 overexpression, we found that NUP62 helps alleviate senescence in HDPSCs by enhancing the nuclear transport of the transcription factor E2F1. This, in turn, stimulates the transcription of the epigenetic enzyme NSD2. Finally, the overexpression of NUP62 influences the H3K36me2 and H3K36me3 modifications of anti-aging genes (HMGA1, HMGA2, and SIRT6). Our results demonstrated that NUP62 regulates the fate of HDPSCs via NSD2-dependent epigenetic reprogramming. |
| format | Article |
| id | doaj-art-798c39d90ed74d4bb89c190942c0f5de |
| institution | OA Journals |
| issn | 2049-3169 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | International Journal of Oral Science |
| spelling | doaj-art-798c39d90ed74d4bb89c190942c0f5de2025-08-20T02:30:20ZengNature Publishing GroupInternational Journal of Oral Science2049-31692025-04-0117111210.1038/s41368-025-00362-yNUP62 alleviates senescence and promotes the stemness of human dental pulp stem cells via NSD2-dependent epigenetic reprogrammingXiping Wang0Li Wang1Linxi Zhou2Lu Chen3Jiayi Shi4Jing Ge5Sha Tian6Zihan Yang7Yuqiong Zhou8Qihao Yu9Jiacheng Jin10Chen Ding11Yihuai Pan12Duohong Zou13School and Hospital of Stomatology, Wenzhou Medical UniversitySchool and Hospital of Stomatology, Wenzhou Medical UniversityDepartment of Orthodontics, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine; College of Stomatology, Shanghai Jiao Tong University; National Center for Stomatology; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of StomatologyDepartment of Oral Surgery, Shanghai Ninth People’s Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology and Shanghai Research Institute of StomatologySchool and Hospital of Stomatology, Wenzhou Medical UniversityDepartment of Oral Surgery, Shanghai Ninth People’s Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology and Shanghai Research Institute of StomatologyState Key Laboratory of Genetic Engineering, School of Life Sciences, Human Phenome Institute, Fudan UniversitySchool and Hospital of Stomatology, Wenzhou Medical UniversityDepartment of Oral Surgery, Shanghai Ninth People’s Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology and Shanghai Research Institute of StomatologySchool and Hospital of Stomatology, Wenzhou Medical UniversityTouro College of Dental Medicine, New York Medical CollegeState Key Laboratory of Genetic Engineering, School of Life Sciences, Human Phenome Institute, Fudan UniversitySchool and Hospital of Stomatology, Wenzhou Medical UniversitySchool and Hospital of Stomatology, Wenzhou Medical UniversityAbstract Stem cells play a crucial role in maintaining tissue regenerative capacity and homeostasis. However, mechanisms associated with stem cell senescence require further investigation. In this study, we conducted a proteomic analysis of human dental pulp stem cells (HDPSCs) obtained from individuals of various ages. Our findings showed that the expression of NUP62 was decreased in aged HDPSCs. We discovered that NUP62 alleviated senescence-associated phenotypes and enhanced differentiation potential both in vitro and in vivo. Conversely, the knocking down of NUP62 expression aggravated the senescence-associated phenotypes and impaired the proliferation and migration capacity of HDPSCs. Through RNA-sequence and decoding the epigenomic landscapes remodeled induced by NUP62 overexpression, we found that NUP62 helps alleviate senescence in HDPSCs by enhancing the nuclear transport of the transcription factor E2F1. This, in turn, stimulates the transcription of the epigenetic enzyme NSD2. Finally, the overexpression of NUP62 influences the H3K36me2 and H3K36me3 modifications of anti-aging genes (HMGA1, HMGA2, and SIRT6). Our results demonstrated that NUP62 regulates the fate of HDPSCs via NSD2-dependent epigenetic reprogramming.https://doi.org/10.1038/s41368-025-00362-y |
| spellingShingle | Xiping Wang Li Wang Linxi Zhou Lu Chen Jiayi Shi Jing Ge Sha Tian Zihan Yang Yuqiong Zhou Qihao Yu Jiacheng Jin Chen Ding Yihuai Pan Duohong Zou NUP62 alleviates senescence and promotes the stemness of human dental pulp stem cells via NSD2-dependent epigenetic reprogramming International Journal of Oral Science |
| title | NUP62 alleviates senescence and promotes the stemness of human dental pulp stem cells via NSD2-dependent epigenetic reprogramming |
| title_full | NUP62 alleviates senescence and promotes the stemness of human dental pulp stem cells via NSD2-dependent epigenetic reprogramming |
| title_fullStr | NUP62 alleviates senescence and promotes the stemness of human dental pulp stem cells via NSD2-dependent epigenetic reprogramming |
| title_full_unstemmed | NUP62 alleviates senescence and promotes the stemness of human dental pulp stem cells via NSD2-dependent epigenetic reprogramming |
| title_short | NUP62 alleviates senescence and promotes the stemness of human dental pulp stem cells via NSD2-dependent epigenetic reprogramming |
| title_sort | nup62 alleviates senescence and promotes the stemness of human dental pulp stem cells via nsd2 dependent epigenetic reprogramming |
| url | https://doi.org/10.1038/s41368-025-00362-y |
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