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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 (
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
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