Please use this identifier to cite or link to this item:
http://hdl.handle.net/10397/81734
| Title: | KDM3A and KDM4C regulate mesenchymal stromal cell senescence and bone aging via condensin-mediated heterochromatin reorganization | Authors: | Huang, B Wang, B Lee, WYW Pong, UK Leung, KT Li, XC Liu, ZQ Chen, R Lin, JC Tsang, LL Liu, BH Ruan, YC Chan, HC Li, G Jiang, XH |
Issue Date: | 2019 | Source: | iScience, 22 Nov. 2019, v. 21, p. 375-390 | Abstract: | 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. | Publisher: | Cell Press | Journal: | iScience | EISSN: | 2589-0042 | DOI: | 10.1016/j.isci.2019.10.041 | Rights: | © 2019 The Author(s). This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). The following publication Huang, B., Wang, B., Lee, W. Y. W., Pong, U. K., Leung, K. T., Li, X. C., . . . Jiang, X. H. (2019). KDM3A and KDM4C regulate mesenchymal stromal cell senescence and bone aging via condensin-mediated heterochromatin reorganization. iScience, 21, 375-390 is available at https://dx.doi.org/10.1016/j.isci.2019.10.041 |
| Appears in Collections: | Journal/Magazine Article |
Files in This Item:
| File | Description | Size | Format | |
|---|---|---|---|---|
| Huang_KDM3A_KDM4C_Regulate.pdf | 9.6 MB | Adobe PDF | View/Open |
Access
View full-text via PolyU eLinks 
Page views
65
Last Week
1
1
Last month
Citations as of Jun 4, 2023
Downloads
103
Citations as of Jun 4, 2023
SCOPUSTM
Citations
28
Citations as of Jun 8, 2023
WEB OF SCIENCETM
Citations
27
Citations as of Jun 8, 2023
Google ScholarTM
Check
Altmetric
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.