人类大脑单细胞染色质可及性比较图谱。
A comparative atlas of single-cell chromatin accessibility in the human brain.
机构信息
Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
Center for Epigenomics, University of California San Diego, School of Medicine, La Jolla, CA 92093, USA.
出版信息
Science. 2023 Oct 13;382(6667):eadf7044. doi: 10.1126/science.adf7044.
Recent advances in single-cell transcriptomics have illuminated the diverse neuronal and glial cell types within the human brain. However, the regulatory programs governing cell identity and function remain unclear. Using a single-nucleus assay for transposase-accessible chromatin using sequencing (snATAC-seq), we explored open chromatin landscapes across 1.1 million cells in 42 brain regions from three adults. Integrating this data unveiled 107 distinct cell types and their specific utilization of 544,735 candidate cis-regulatory DNA elements (cCREs) in the human genome. Nearly a third of the cCREs demonstrated conservation and chromatin accessibility in the mouse brain cells. We reveal strong links between specific brain cell types and neuropsychiatric disorders including schizophrenia, bipolar disorder, Alzheimer's disease (AD), and major depression, and have developed deep learning models to predict the regulatory roles of noncoding risk variants in these disorders.
单细胞转录组学的最新进展揭示了人类大脑中多样化的神经元和神经胶质细胞类型。然而，调控细胞身份和功能的调控程序仍不清楚。我们使用基于转座酶可及染色质测序的单细胞核分析（snATAC-seq）方法，在来自 3 名成年人的 42 个脑区的 110 万个细胞中探索了开放染色质图谱。整合这些数据揭示了 107 种不同的细胞类型，以及它们在人类基因组中 544735 个候选顺式调控 DNA 元件（cCREs）的特定利用。近三分之一的 cCREs 在小鼠大脑细胞中具有保守性和染色质可及性。我们揭示了特定脑区细胞类型与精神神经疾病（包括精神分裂症、双相情感障碍、阿尔茨海默病和重度抑郁症）之间的紧密联系，并开发了深度学习模型来预测这些疾病中非编码风险变异的调控作用。
Zotero 插件