美国加州大学圣迭戈分校任兵团队绘制出人脑中单细胞染色质可及性的比较图谱。该项研究成果发表在2023年10月13日出版的《科学》上。

利用通过测序的转座酶可及染色质（snATAC-seq）的单核分析，研究人员探索了来自3名成年人的42个大脑区域的110万个细胞的开放染色质景观。整合这些数据揭示了107种不同的细胞类型及其对人类基因组中544735个候选顺式调控DNA元件（cCRE）的特异性利用。近三分之一的cCRE在单核细胞中表现出保守性和染色质可及性。研究人员揭示了特定脑细胞类型与神经精神疾病（包括精神分裂症、双相情感障碍、阿尔茨海默病（AD）和重度抑郁症）之间的密切联系，并开发了深度学习模型来预测非编码风险变异在这些疾病中的调节作用。

据了解，单细胞转录组学的最新进展揭示了人类大脑中不同的神经元和胶质细胞类型。然而，调控细胞身份和功能的调控程序仍不清楚。

附：英文原文

Title: A comparative atlas of single-cell chromatin accessibility in the human brain

Author: Yang Eric Li, Sebastian Preissl, Michael Miller, Nicholas D. Johnson, Zihan Wang, Henry Jiao, Chenxu Zhu, Zhaoning Wang, Yang Xie, Olivier Poirion, Colin Kern, Antonio Pinto-Duarte, Wei Tian, Kimberly Siletti, Nora Emerson, Julia Osteen, Jacinta Lucero, Lin Lin, Qian Yang, Quan Zhu, Nathan Zemke, Sarah Espinoza, Anna Marie Yanny, Julie Nyhus, Nick Dee, Tamara Casper, Nadiya Shapovalova, Daniel Hirschstein, Rebecca D. Hodge, Sten Linnarsson, Trygve Bakken, Boaz Levi, C. Dirk Keene, Jingbo Shang, Ed Lein, Allen Wang, M. Margarita Behrens, Joseph R. Ecker, Bing Ren

Issue&Volume: 2023-10-13

Abstract: 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.

DOI: adf7044

Source: https://www.science.org/doi/10.1126/science.adf7044

期刊信息

Science：《科学》，创刊于1880年。隶属于美国科学促进会，最新IF：63.714

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