Scholarlink

<p>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 <i>GABRA2</i>, <i>GRM8</i>, and <i>NCAM1</i> and show significant enrichment for AUD risk genes within these DEGs. We identified 51,431 cell type-specific, disease associated candidate <i>cis</i>-regulatory elements including an interneuron-associated set of chromatin loops at the AUD risk gene <i>CALN1</i>. 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.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

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

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年1月19日

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

摘要

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.