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KDM3A and KDM4C Regulate Mesenchymal Stromal Cell Senescence and Bone Aging via Condensin-mediated Heterochromatin Reorganization.
Huang, Biao; Wang, Bin; Yuk-Wai Lee, Wayne; Pong U, Kin; Leung, Kam Tong; Li, Xican; Liu, Zhenqing; Chen, Rui; Lin, Jia Cheng; Tsang, Lai Ling; Liu, Baohua; Ruan, Ye Chun; Chan, Hsiao Chang; Li, Gang; Jiang, Xiaohua.
Afiliação
  • Huang B; Key Laboratory for Regenerative Medicine of the Ministry of Education of China, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Room 409A, Lo Kwee Seong Integrated Biomedical Sciences Building, Area 39, Shatin, Hong Kong SAR, PR China; The Chinese University
  • Wang B; The Chinese University of Hong Kong, Shenzhen Research Institute, Shenzhen, PR China; Department of Orthopaedics & Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, PR China.
  • Yuk-Wai Lee W; The Chinese University of Hong Kong, Shenzhen Research Institute, Shenzhen, PR China; Department of Orthopaedics & Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, PR China.
  • Pong U K; Key Laboratory for Regenerative Medicine of the Ministry of Education of China, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Room 409A, Lo Kwee Seong Integrated Biomedical Sciences Building, Area 39, Shatin, Hong Kong SAR, PR China; The Chinese University
  • Leung KT; Department of Pediatrics, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, PR China.
  • Li X; School of Chinese Herbal Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510006, China; Innovative Research & Development Laboratory of TCM, Guangzhou University of Chinese Medicine, Guangzhou 510006, China.
  • Liu Z; Key Laboratory for Regenerative Medicine of the Ministry of Education of China, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Room 409A, Lo Kwee Seong Integrated Biomedical Sciences Building, Area 39, Shatin, Hong Kong SAR, PR China.
  • Chen R; Key Laboratory for Regenerative Medicine of the Ministry of Education of China, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Room 409A, Lo Kwee Seong Integrated Biomedical Sciences Building, Area 39, Shatin, Hong Kong SAR, PR China.
  • Lin JC; Key Laboratory for Regenerative Medicine of the Ministry of Education of China, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Room 409A, Lo Kwee Seong Integrated Biomedical Sciences Building, Area 39, Shatin, Hong Kong SAR, PR China; The Chinese University
  • Tsang LL; Key Laboratory for Regenerative Medicine of the Ministry of Education of China, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Room 409A, Lo Kwee Seong Integrated Biomedical Sciences Building, Area 39, Shatin, Hong Kong SAR, PR China; The Chinese University
  • Liu B; Shenzhen University Health Science Center, Shenzhen University, Shenzhen, PR China.
  • Ruan YC; Department of Biomedical Engineering, The Hong Kong Polytechnic University, Hong Kong, PR China.
  • Chan HC; Key Laboratory for Regenerative Medicine of the Ministry of Education of China, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Room 409A, Lo Kwee Seong Integrated Biomedical Sciences Building, Area 39, Shatin, Hong Kong SAR, PR China; The Chinese University
  • Li G; The Chinese University of Hong Kong, Shenzhen Research Institute, Shenzhen, PR China; Department of Orthopaedics & Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, PR China.
  • Jiang X; Key Laboratory for Regenerative Medicine of the Ministry of Education of China, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Room 409A, Lo Kwee Seong Integrated Biomedical Sciences Building, Area 39, Shatin, Hong Kong SAR, PR China; The Chinese University
iScience ; 21: 375-390, 2019 Nov 22.
Article em En | MEDLINE | ID: mdl-31704649
Epigenomic changes and stem cell deterioration are two hallmarks of aging. Accumulating evidence suggest that senescence of mesenchymal stromal cells (MSCs) perpetuates aging or age-related diseases. Here we report that two H3K9 demethylases, KDM3A and KDM4C, regulate heterochromatin reorganization via transcriptionally activating condensin components NCAPD2 and NCAPG2 during MSC senescence. Suppression of KDM3A or KDM4C by either genetic or biochemical approach leads to robust DNA damage response and aggravates cellular senescence, whereas overexpression of KDM3A/KDM4C or NCAPD2 promotes heterochromatin reorganization and blunts DNA damage response. Moreover, MSCs derived from Kdm3a-/- mice exhibit defective chromosome organization and exacerbated DNA damage response, which are associated with accelerated bone aging. Consistently, analysis of human bone marrow MSCs and transcriptome database reveals inverse correlation of KDM3A/KDM4C and/or NCAPD2/NCAPG2 with aging. Taken together, the present finding unveils that H3K9 demethylases function as a surveillance mechanism to restrain DNA damage accumulation in stem cells during aging.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: IScience Ano de publicação: 2019 Tipo de documento: Article País de publicação: Estados Unidos
Texto completo
Adicionar na Minha BVS
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PubMed Links
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: IScience Ano de publicação: 2019 Tipo de documento: Article País de publicação: Estados Unidos