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

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

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Autistic spectrum disorder(ASD)is a male-biased,heterogeneous neurodevelopmental disorder that af-fects 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 aim 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 are 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 are analyzed,and the largest number of differentially expressed genes(DEGs)are found in neurons,choroid plexus epithelial cells,and microglia.In microglia,several pathways related to inflammation are found in both males and females,including the tumor necrosis factor(TNF),nuclear factor kappa B(NF-KB),toll-like receptor(TLR),and mitogen-activated protein kinase(MAPK)signaling pathways,which are important for the induction of autistic-like behavior.Additionally,we note 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 mice.The elucidation of sexual differences could provide innovative strategies for the prevention and treatment of ASD.

Autistic spectrum disorder(ASD)SexSingle cellNeuronsMicroglia

Qian Zhang、Yongjie Wang、Jie Tao、Ruixue Xia、Yijie Zhang、Zhirui Liu、Jiwei Cheng

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Department of Neurology and Central Laboratory,Putuo Hospital,Shanghai University of Traditional Chinese Medicine,Shanghai 200062,China

School of Pharmacy,Hangzhou Normal University,Hangzhou,Zhejiang 311121,China

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

国家自然科学基金国家自然科学基金Project for Capacity Promotion of Putuo District Clinical Special Disease"Stroke"science and Technology Innovation Project of Putuo District Health Systemscience and Technology Innovation Project of Putuo District Health SystemTraining Plan of"100 professionals"of Shanghai Putuo District Central HospitalProject of"XingLin Scholars Training"of Chengdu University of Traditional Chinese MedicineShanghai Putuo District Health System Clinical Characteristic Special Disease Construction Project

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2024

10.1016/j.jgg.2023.08.012

遗传学报
中国遗传学会 中国科学院遗传与发育生物学研究所

遗传学报

CSTPCD
影响因子：0.821
ISSN：1673-8527
年,卷(期)：2024.51(3)
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