2. Academic Validation
  3. Sex-biased single cell genetic landscape in mice with autism spectrum disorder

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

  • J Genet Genomics. 2023 Sep 11;S1673-8527(23)00184-4. doi: 10.1016/j.jgg.2023.08.012.
Qian Zhang 1,  Yongjie Wang 2,  Jie Tao 1,  Ruixue Xia 3,  Yijie Zhang 3,  Zhirui Liu 4,  Jiwei Cheng 5
Affiliations

Affiliations

  • 1 Department of Neurology and Central Laboratory,Putuo Hospital,Shanghai University of Traditional Chinese Medicine,Shanghai 200062,China.
  • 2 School of Pharmacy,Hangzhou Normal University,Hangzhou,Jiangsu 310030,China.
  • 3 Department of Respiratory and Critical Care Medicine,Henan University Huaihe Hospital,Kaifeng,Henan 475099,China.
  • 4 Department of Neurology and Central Laboratory,Putuo Hospital,Shanghai University of Traditional Chinese Medicine,Shanghai 200062,China. Electronic address: [email protected].
  • 5 Department of Neurology and Central Laboratory,Putuo Hospital,Shanghai University of Traditional Chinese Medicine,Shanghai 200062,China. Electronic address: [email protected].
PMID: 37703921 DOI: 10.1016/j.jgg.2023.08.012
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.

Keywords

Autistic spectrum disorder (ASD); microglia; neurons; sex; single cell.

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