韩国大田基础科学研究所Junyeop Daniel Roh研究团队取得一项新突破。他们的研究开发出了asd风险突变小鼠的转录组分类。该研究于2026年9月17日发表于国际一流学术期刊《科学》杂志上。

自闭症谱系障碍（ASD）是一种具有强烈遗传因素的神经发育疾病。大规模人类遗传学研究已鉴定出超过1200个ASD风险基因。研究人员报道了一个性别平衡的图谱，包含来自17个携带ASD风险突变小鼠品系的1008份前额叶RNA测序（RNA-seq）图谱。他们的分析识别出两种相反的转录组状态。这两组在性别偏倚、区域特异性、发育稳定性、细胞类型重塑以及对氟西汀和锂的响应方面存在差异。单核RNA-seq显示，第1组比第2组具有更广泛的细胞类型重塑，并且细胞类型特异性模块显示出相互关联，反映了整体转录组特征。该框架对独立小鼠品系进行分类，并识别出具有保守突触方向性的亚组，支持分子分层。

附：英文原文

Title: Transcriptome-based classification in mice with ASD-risk mutations

Author: 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, 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 Bae, Eunjoon Kim

Issue&Volume: 2026-09-17

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.

DOI: 10.1126/science.adz6688

Source: https://www.science.org/doi/10.1126/science.adz6688