NUP62 alleviates senescence and promotes the stemness of human dental pulp stem cells via NSD2-dependent epigenetic reprogramming.
10.1038/s41368-025-00362-y
- Author:
Xiping WANG
1
;
Li WANG
1
;
Linxi ZHOU
2
;
Lu CHEN
3
;
Jiayi SHI
1
;
Jing GE
3
;
Sha TIAN
4
;
Zihan YANG
1
;
Yuqiong ZHOU
3
;
Qihao YU
1
;
Jiacheng JIN
5
;
Chen DING
4
;
Yihuai PAN
6
;
Duohong ZOU
7
,
8
Author Information
1. School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou, China.
2. Department 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 Stomatology, Shanghai, China.
3. Department 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 Stomatology, Shanghai, China.
4. State Key Laboratory of Genetic Engineering, School of Life Sciences, Human Phenome Institute, Fudan University, Shanghai, China.
5. Touro College of Dental Medicine, New York Medical College, New York, USA.
6. School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou, China. yihuaipan@wmu.edu.cn.
7. School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou, China. zouduohongyy@
8. com.
- Publication Type:Research Support, Non-U.S. Gov't
- MeSH:
Humans;
Dental Pulp/cytology*;
Nuclear Pore Complex Proteins/genetics*;
Cellular Senescence/genetics*;
Stem Cells/metabolism*;
Epigenesis, Genetic;
Cell Proliferation;
Cell Differentiation;
Histone-Lysine N-Methyltransferase/metabolism*;
Cells, Cultured;
Cellular Reprogramming;
Cell Movement;
Proteomics
- From:
International Journal of Oral Science
2025;17(1):34-34
- CountryChina
- Language:English
-
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.
