Acetate supplementation restores cognitive deficits caused by ARID1A haploinsufficiency in excitatory neurons
Abstract: Mutations in AT‐rich interactive domain‐containing protein 1A (ARID1A) cause Coffin‐Siris syndrome (CSS), a rare genetic disorder that results in mild to severe intellectual disabilities. However, the biological role of ARID1A in the brain remains unclear. In this study, we report that the haploinsufficiency of ARID1A in excitatory neurons causes cognitive impairment and defects in hippocampal synaptic transmission and dendritic morphology in mice. Similarly, human embryonic stem cell‐derived excitatory neurons with deleted ARID1A exhibit fewer dendritic branches and spines, and abnormal electrophysiological activity. Importantly, supplementation of acetate, an epigenetic metabolite, can ameliorate the morphological and electrophysiological deficits observed in mice with Arid1a haploinsufficiency, as well as in ARID1A‐null human excitatory neurons. Mechanistically, transcriptomic and ChIP‐seq analyses demonstrate that acetate supplementation can increase the levels of H3K27 acetylation at the promoters of key regulatory genes associated with neural development and synaptic transmission. Collectively, these findings support the essential roles of ARID1A in the excitatory neurons and cognition and suggest that acetate supplementation could be a potential therapeutic intervention for CSS.
- Location
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Deutsche Nationalbibliothek Frankfurt am Main
- Extent
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Online-Ressource
- Language
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Englisch
- Bibliographic citation
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Acetate supplementation restores cognitive deficits caused by ARID1A haploinsufficiency in excitatory neurons ; day:17 ; month:11 ; year:2022 ; extent:20
EMBO molecular medicine / European Molecular Biology Organization ; (17.11.2022) (gesamt 20)
- Creator
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Liu, Pei‐Pei
Dai, Shang‐Kun
Mi, Ting‐Wei
Tang, Gang‐Bin
Wang, Zhuo
Wang, Hui
Du, Hong‐Zhen
Tang, Yi
Teng, Zhao‐Qian
Liu, Chang‐Mei
- DOI
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10.15252/emmm.202215795
- URN
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urn:nbn:de:101:1-2022111714165187515647
- Rights
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Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Last update
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15.08.2025, 7:30 AM CEST
Data provider
Deutsche Nationalbibliothek. If you have any questions about the object, please contact the data provider.
Associated
- Liu, Pei‐Pei
- Dai, Shang‐Kun
- Mi, Ting‐Wei
- Tang, Gang‐Bin
- Wang, Zhuo
- Wang, Hui
- Du, Hong‐Zhen
- Tang, Yi
- Teng, Zhao‐Qian
- Liu, Chang‐Mei
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