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Nature communications · 2026

Central amygdala single-nucleus atlas reveals chromatin and gene transcription dynamics in human alcohol use disorder.

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Lee Che Yu, Hwang Ahyeon, McRiley Delaney, Lee Jaywon, Thibodeau Genevieve, Duman Catharine, Zhang Xiangyu, Skarica Mario, Coudriet Jensine, Xu Siwei, Terwilliger Rosemarie, Sliby Alexa-Nicole, Wang Jiawei, Nguyen Tuan, Liu Yujing, Li Hongyu, Dai Yi, Duan Ziheng, Lei Yutong, Lin Yingxin, Glausier Jill R, Lewis David A, Gelernter Joel, Holtzheimer Paul E, Xu Ke, Zhou Hang, Zhao Hongyu, Thompson Summer L, Krystal John H, Che Alicia, Taylor Jane R, Zhang Jing, Girgenti Matthew J

Аннотация

Regulation of gene expression is a highly coordinated process in both the healthy and pathological brain with unique patterns across a multitude of cell types. Here we present a multi-omic single nucleus study of ~175,000 nuclei from 50 donors with alcohol use disorder (AUD) and control donors without AUD, profiling cell type specific gene expression and chromatin accessibility in the human central amygdala. We identify all major CNS cell types and neuronal subtypes and find inhibitory neurons are particularly affected by AUD. We find high numbers of differentially expressed genes (DEGs) including GABRA2, GRM8, and NCAM1 and show significant enrichment for AUD risk genes within these DEGs. We identified 51,431 cell type-specific, disease associated candidate cis-regulatory elements including an interneuron-associated set of chromatin loops at the AUD risk gene CALN1. Transcription factor footprinting identified Kruppel-like factors upstream of AUD GWAS genes and DEGs. Finally, we also perform cell type-specific fine mapping for AUD GWAS to prioritize variants within functional genomic elements.

Предметные рубрики MeSH

ИП Урсолов Владлен Сергеевич

ИНН 500118482352 · ОГРНИП 314500117700049

Реквизиты и контакты