KDM3A and KDM4C Regulate Mesenchymal Stromal Cell Senescence and Bone Aging via Condensin-mediated Heterochromatin Reorganization
Summary: 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 reorga...
| Main Authors: | , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2019-11-01
|
| Series: | iScience |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004219304213 |
| id |
doaj-bd0253eb567e4c14a2e4be4b3ba4d30d |
|---|---|
| record_format |
Article |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Biao Huang Bin Wang Wayne Yuk-Wai Lee Kin Pong U Kam Tong Leung Xican Li Zhenqing Liu Rui Chen Jia cheng Lin Lai Ling Tsang Baohua Liu Ye chun Ruan Hsiao Chang Chan Gang Li Xiaohua Jiang |
| spellingShingle |
Biao Huang Bin Wang Wayne Yuk-Wai Lee Kin Pong U Kam Tong Leung Xican Li Zhenqing Liu Rui Chen Jia cheng Lin Lai Ling Tsang Baohua Liu Ye chun Ruan Hsiao Chang Chan Gang Li Xiaohua Jiang KDM3A and KDM4C Regulate Mesenchymal Stromal Cell Senescence and Bone Aging via Condensin-mediated Heterochromatin Reorganization iScience |
| author_facet |
Biao Huang Bin Wang Wayne Yuk-Wai Lee Kin Pong U Kam Tong Leung Xican Li Zhenqing Liu Rui Chen Jia cheng Lin Lai Ling Tsang Baohua Liu Ye chun Ruan Hsiao Chang Chan Gang Li Xiaohua Jiang |
| author_sort |
Biao Huang |
| title |
KDM3A and KDM4C Regulate Mesenchymal Stromal Cell Senescence and Bone Aging via Condensin-mediated Heterochromatin Reorganization |
| title_short |
KDM3A and KDM4C Regulate Mesenchymal Stromal Cell Senescence and Bone Aging via Condensin-mediated Heterochromatin Reorganization |
| title_full |
KDM3A and KDM4C Regulate Mesenchymal Stromal Cell Senescence and Bone Aging via Condensin-mediated Heterochromatin Reorganization |
| title_fullStr |
KDM3A and KDM4C Regulate Mesenchymal Stromal Cell Senescence and Bone Aging via Condensin-mediated Heterochromatin Reorganization |
| title_full_unstemmed |
KDM3A and KDM4C Regulate Mesenchymal Stromal Cell Senescence and Bone Aging via Condensin-mediated Heterochromatin Reorganization |
| title_sort |
kdm3a and kdm4c regulate mesenchymal stromal cell senescence and bone aging via condensin-mediated heterochromatin reorganization |
| publisher |
Elsevier |
| series |
iScience |
| issn |
2589-0042 |
| publishDate |
2019-11-01 |
| description |
Summary: 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. : Molecular Mechanism of Gene Regulation; Cell Biology; Stem Cells Research Keywords: mesenchymal stromal cells, condensin, histone demethylase, DNA damage, bone aging, epigenetic regulation, Subject Areas: Molecular Mechanism of Gene Regulation, Cell Biology, Stem Cells Research |
| url |
http://www.sciencedirect.com/science/article/pii/S2589004219304213 |
| work_keys_str_mv |
AT biaohuang kdm3aandkdm4cregulatemesenchymalstromalcellsenescenceandboneagingviacondensinmediatedheterochromatinreorganization AT binwang kdm3aandkdm4cregulatemesenchymalstromalcellsenescenceandboneagingviacondensinmediatedheterochromatinreorganization AT wayneyukwailee kdm3aandkdm4cregulatemesenchymalstromalcellsenescenceandboneagingviacondensinmediatedheterochromatinreorganization AT kinpongu kdm3aandkdm4cregulatemesenchymalstromalcellsenescenceandboneagingviacondensinmediatedheterochromatinreorganization AT kamtongleung kdm3aandkdm4cregulatemesenchymalstromalcellsenescenceandboneagingviacondensinmediatedheterochromatinreorganization AT xicanli kdm3aandkdm4cregulatemesenchymalstromalcellsenescenceandboneagingviacondensinmediatedheterochromatinreorganization AT zhenqingliu kdm3aandkdm4cregulatemesenchymalstromalcellsenescenceandboneagingviacondensinmediatedheterochromatinreorganization AT ruichen kdm3aandkdm4cregulatemesenchymalstromalcellsenescenceandboneagingviacondensinmediatedheterochromatinreorganization AT jiachenglin kdm3aandkdm4cregulatemesenchymalstromalcellsenescenceandboneagingviacondensinmediatedheterochromatinreorganization AT lailingtsang kdm3aandkdm4cregulatemesenchymalstromalcellsenescenceandboneagingviacondensinmediatedheterochromatinreorganization AT baohualiu kdm3aandkdm4cregulatemesenchymalstromalcellsenescenceandboneagingviacondensinmediatedheterochromatinreorganization AT yechunruan kdm3aandkdm4cregulatemesenchymalstromalcellsenescenceandboneagingviacondensinmediatedheterochromatinreorganization AT hsiaochangchan kdm3aandkdm4cregulatemesenchymalstromalcellsenescenceandboneagingviacondensinmediatedheterochromatinreorganization AT gangli kdm3aandkdm4cregulatemesenchymalstromalcellsenescenceandboneagingviacondensinmediatedheterochromatinreorganization AT xiaohuajiang kdm3aandkdm4cregulatemesenchymalstromalcellsenescenceandboneagingviacondensinmediatedheterochromatinreorganization |
| _version_ |
1725116451184967680 |
| spelling |
doaj-bd0253eb567e4c14a2e4be4b3ba4d30d2020-11-25T01:24:53ZengElsevieriScience2589-00422019-11-0121375390KDM3A and KDM4C Regulate Mesenchymal Stromal Cell Senescence and Bone Aging via Condensin-mediated Heterochromatin ReorganizationBiao Huang0Bin Wang1Wayne Yuk-Wai Lee2Kin Pong U3Kam Tong Leung4Xican Li5Zhenqing Liu6Rui Chen7Jia cheng Lin8Lai Ling Tsang9Baohua Liu10Ye chun Ruan11Hsiao Chang Chan12Gang Li13Xiaohua Jiang14Key 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 of Hong Kong, Shenzhen Research Institute, Shenzhen, PR ChinaThe 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 ChinaThe 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 ChinaKey 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 of Hong Kong, Shenzhen Research Institute, Shenzhen, PR ChinaDepartment of Pediatrics, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, PR ChinaSchool 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, ChinaKey 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 ChinaKey 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 ChinaKey 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 of Hong Kong, Shenzhen Research Institute, Shenzhen, PR ChinaKey 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 of Hong Kong, Shenzhen Research Institute, Shenzhen, PR ChinaShenzhen University Health Science Center, Shenzhen University, Shenzhen, PR ChinaDepartment of Biomedical Engineering, The Hong Kong Polytechnic University, Hong Kong, PR ChinaKey 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 of Hong Kong, Shenzhen Research Institute, Shenzhen, PR ChinaThe 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 ChinaKey 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 of Hong Kong, Shenzhen Research Institute, Shenzhen, PR China; Corresponding authorSummary: 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. : Molecular Mechanism of Gene Regulation; Cell Biology; Stem Cells Research Keywords: mesenchymal stromal cells, condensin, histone demethylase, DNA damage, bone aging, epigenetic regulation, Subject Areas: Molecular Mechanism of Gene Regulation, Cell Biology, Stem Cells Researchhttp://www.sciencedirect.com/science/article/pii/S2589004219304213 |