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Article Navigation >  Journal of Genetics and Genomics  > 2023  > Accepted Manuscript

Sex-biased single cell genetic landscape in mice with autism spectrum disorder

doi: 10.1016/j.jgg.2023.08.012
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    a Department of Neurology and Central Laboratory, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, China;

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    b School of Pharmacy, Hangzhou Normal University, Hangzhou, Jiangsu 310030, China;

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    c Department of Respiratory and Critical Care Medicine, Henan University Huaihe Hospital, Kaifeng, Henan 475099, China

Funds:

This work was supported by the National Natural Science Foundation of China (Nos. 82074162 and 82274344), Project for Capacity Promotion of Putuo District Clinical Special Disease “Stroke”, Science and Technology Innovation Project of Putuo District Health System (Nos. ptkwws201902 and ptkwws202301), Training Plan of “100 professionals” of Shanghai Putuo District Central Hospital（ 2022-RCJC-05）, Project of “XingLin Scholars Training” of Chengdu University of Traditional Chinese Medicine (No. YYZX2022170), and Shanghai Putuo District Health System Clinical Characteristic Special Disease Construction Project (No. 2023tszb04).

  • Received Date: 2023-08-22
  • Revised Date: 2023-08-30
    • Available Online: 2023-09-13
    Abstract
  • Autistic spectrum disorder (ASD) is a male-biased heterogeneous neurodevelopmental disorder that affects approximately 1%–2% of the population. Prenatal exposure to valproic acid (VPA) is a recognized risk factor for ASD, but the cellular and molecular basis of VPA-induced ASD at the single-cell resolution is unclear. Here, we aimed to compare the cellular and molecular differences in the hippocampus between male and female prenatal mice with ASD at the single-cell transcriptomic level. The transcriptomes of more than 45,000 cells were assigned to 12 major cell types, including neurons, glial cells, vascular cells, and immune cells. Cell type-specific genes with altered expression after prenatal VPA exposure were analyzed, and the largest number of differentially expressed genes (DEGs) were found in neurons, choroid plexus epithelial cells, and microglia. In microglia, several pathways related to inflammation were found in both males and females, including the TNF, NF-κB, Toll-like receptor, and MAPK signaling pathways, which are important for the induction of autistic-like behavior. Additionally, we noted that several X-linked genes, including Bex1, Bex3, and Gria3, were among the male-specific DEGs of neurons. This pioneering study describes the landscape of the transcriptome in the hippocampus of autistic individuals. The elucidation of sexual differences could provide innovative strategies for the prevention and treatment of ASD.
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