Transcriptome-based classification in mice with ASD-risk mutations
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.
Authors
- Yunho Yi
- Yeonghyeon Kim (ORCID: https://orcid.org/0000-0001-8074-6598)
- Eunjoon Kim (ORCID: https://orcid.org/0000-0001-5518-6584)
- Muwon Kang (ORCID: https://orcid.org/0000-0001-7136-5865)
- Jeseung Ryu (ORCID: https://orcid.org/0000-0002-2544-3727)
- Taesun Yoo (ORCID: https://orcid.org/0000-0002-7315-0785)
- Seongbin Kim (ORCID: https://orcid.org/0009-0000-1105-5558)
- Sunjoo Ahn (ORCID: https://orcid.org/0000-0002-6519-6492)
- Yeji Yang (ORCID: https://orcid.org/0000-0002-2994-4510)
- Junyeop Daniel Roh (ORCID: https://orcid.org/0000-0001-5831-473X)
- Hyosang Kim (ORCID: https://orcid.org/0000-0003-1275-2819)
- Hyoseon Oh (ORCID: https://orcid.org/0000-0003-1713-2707)
- Yukyung Jun (ORCID: https://orcid.org/0000-0002-4025-7164)
- Junyoung Kim (ORCID: https://orcid.org/0000-0002-3574-6908)
- Jin Young Kim (ORCID: https://orcid.org/0000-0002-0656-1269)
- Hyojin Kang (ORCID: https://orcid.org/0000-0002-3403-276X)
- Heejin Cho (ORCID: https://orcid.org/0000-0003-4041-8033)
- Heera Moon
- Mihyun Bae (ORCID: https://orcid.org/0000-0001-8961-3396)
- Chunmei Jin (ORCID: https://orcid.org/0000-0002-0912-1031)
- Yewon Jung (ORCID: https://orcid.org/0009-0001-4498-7084)
- Jisoo Kim (ORCID: https://orcid.org/0009-0008-7824-2567)
- Jinkyeong Kim (ORCID: https://orcid.org/0009-0002-3675-769X)
- Gahyeon Choi
- Yusang Oh
- Minji Kim
- Heesu Jeon (ORCID: https://orcid.org/0009-0003-1040-6979)
Institutions
- Korea Advanced Institute of Science and Technology (KR)
- Institute for Basic Science (KR)
- Korea Basic Science Institute (KR)
- Korea Research Institute of Chemical Technology (KR)
- Korea Institute of Science & Technology Information (KR)
Publication Details
- Journal
- Science
- Published
- 2026-09-17
- DOI
- https://doi.org/10.1126/science.adz6688
- Citations
- 1
- Primary Topic
- Autism Spectrum Disorder Research
- Type
- article
- Field-Weighted Citation Impact
- 6.13
Funders
- Korea Basic Science Institute
- National Research Foundation of Korea
- Institute for Basic Science
- National Science Foundation, United Arab Emirates