Transcriptome-based classification in mice with ASD-risk mutations

Science 2026

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Authors: Junyeop Daniel Roh, Yukyung Jun, Heesu Jeon, Junyoung Kim, Yunho Yi, Minji Kim, Heejin Cho, Yusang Oh, Heera Moon, Jinkyeong Kim, Seongbin Kim, Jeseung Ryu
+15 more Muwon Kang, Jisoo Kim, Yeonghyeon Kim, Yewon Jung, Taesun Yoo, Hyoseon Oh, Hyosang Kim, Chunmei Jin, Yeji Yang, Gahyeon Choi, Sunjoo Ahn, Jin Young Kim, Hyojin Kang, Mihyun H. Bae, Eunjoon Kim
DOI: 10.1126/science.adz6688
Cited by: 1
References: 72

Abstract

Autism spectrum disorder (ASD) is a neurodevelopmental condition with a strong genetic component. Large-scale human genetic studies have identified >1200 ASD-risk genes. We report a sex-balanced atlas of 1008 prefrontal RNA sequencing (RNA-seq) profiles from 17 mouse lines carrying ASD-risk mutations. Our analysis identified two opposing transcriptomic states. The two groups differed in sex bias, regional specificity, developmental stability, cell type remodeling, and responses to fluoxetine and lithium. Single-nucleus RNA-seq revealed broader cell type remodeling in group 1 than in group 2, and cell type-specific modules showed reciprocal associations that mirrored bulk transcriptomic signatures. The framework classifies independent mouse lines and identifies subgroups with conserved synaptic directionality, supporting molecular stratification.

Fields of Study & Subjects

Autism Spectrum Disorder Research Single-cell and spatial transcriptomics Neurogenesis and neuroplasticity mechanisms

Publication details

Journal / source
Science
Publisher
American Association for the Advancement of Science (AAAS)
Volume
393
Issue
6817
Pages
1250–1257
Publication date
17 September 2026
Language
EN