Single-nucleus transcriptomics reveal disrupted pathways in the prefrontal cortex of Scn2a -deficient mice Article Swipe
Ye-Eun Yoo
,
Purba Mandal
,
Zhengkuan Tang
,
Zaiyang Zhang
,
Jingliang Zhang
,
Xiaoling Chen
,
Morgan Robinson
,
Muriel Eaton
,
Brody Deming
,
Manasi Halurkar
,
Harish Kothandaraman
,
Luke C. Dabin
,
Siyu Jian
,
Hongyu Gao
,
Chongli Yuan
,
Nadia A. Lanman
,
Yunlong Liu
,
Jungsu Kim
,
Priyanka Baloni
,
Yang Yang
·
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1101/2025.09.16.676420
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1101/2025.09.16.676420
Truncating variants in SCN2A , which encodes the NaV1.2 sodium channel critical for action potential initiation and propagation, are associated with autism spectrum disorder (ASD) and epilepsy. To investigate SCN2A deficiency–related phenotypes, we developed a preclinical mouse model with under 50% NaV1.2 expression, exhibiting neuronal hyperexcitability and social deficits. However, the neuronal populations and molecular alterations underlying these phenotypes at single-cell resolution have not been investigated. In this study, we conducted single-nucleus RNA sequencing (snRNA-seq) of wild-type (WT), homozygous Scn2a -deficient (HOM) mice, and HOM mice with Scn2a restoration (HOM-FlpO) to examine the effects of Scn2a level on gene expression in the medial prefrontal cortex (mPFC), a critical brain region related to ASD development. Differential expression analysis in GABAergic and glutamatergic neurons between genotypes revealed gene expression enriched in neurotransmitter activity regulation and synapse organization. Lastly, snRNA-seq results in HOM-FlpO identified genes that were rescued after Scn2a restoration. These results reveal that reduced Scn2a expression disrupts RNA transcriptomes in multiple neuronal subtypes, providing insight into cell type–specific mechanisms underlying SCN2A -related disorders.
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- en
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- https://doi.org/10.1101/2025.09.16.676420
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- References
- 74
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Single-nucleus transcriptomics reveal disrupted pathways in the prefrontal cortex of Scn2a -deficient miceWork title
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preprintOpenAlex work type
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enPrimary language
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2025Year of publication
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2025-09-17Full publication date if available
- Authors
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Ye-Eun Yoo, Purba Mandal, Zhengkuan Tang, Zaiyang Zhang, Jingliang Zhang, Xiaoling Chen, Morgan Robinson, Muriel Eaton, Brody Deming, Manasi Halurkar, Harish Kothandaraman, Luke C. Dabin, Siyu Jian, Hongyu Gao, Chongli Yuan, Nadia A. Lanman, Yunlong Liu, Jungsu Kim, Priyanka Baloni, Yang YangList of authors in order
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https://doi.org/10.1101/2025.09.16.676420Publisher landing page
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https://doi.org/10.1101/2025.09.16.676420Direct OA link when available
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