小柯机器人

美国加州大学Vivek Swarup研究组的最新研究揭示了阿尔茨海默病 (AD) 的单核染色质可及性和转录组学特征。该项研究成果发表在2021年7月8日出版的《自然-遗传学》上。

研究人员报道了针对晚期阿尔茨海默病个体191,890个细胞核的多组学单核研究，分析相同生物样本中的染色质可及性和基因表达，并揭示了明显的细胞异质性；这些结果可通过网站获得。研究人员确定了细胞类型特异性、疾病相关的候选顺式调控元件及其候选靶基因，包括一个由APOE和CLU连接的少突胶质细胞相关调控模块。

研究人员通过全基因组关联研究确定了AD风险位点子集中特定细胞类型的顺式调节关系，证明了这种单核多组学方法的实用性。胶质细胞群的轨迹分析确定了与疾病相关的转录因子，如 SREBF1，及其靶基因。

最后，研究人员采用了单核一致加权基因共表达分析方法对AD转录组进行系统级分析，这是一种对分散单细胞数据共表达网络的分析策略。

据介绍，大脑内的基因调控模式在健康和疾病个体中存在高度动态调控，从而协调不同细胞类型之间的生物过程。

附：英文原文

Title: Single-nucleus chromatin accessibility and transcriptomic characterization of Alzheimer’s disease

Author: Samuel Morabito, Emily Miyoshi, Neethu Michael, Saba Shahin, Alessandra Cadete Martini, Elizabeth Head, Justine Silva, Kelsey Leavy, Mari Perez-Rosendahl, Vivek Swarup

Issue&Volume: 2021-07-08

Abstract: The gene-regulatory landscape of the brain is highly dynamic in health and disease, coordinating a menagerie of biological processes across distinct cell types. Here, we present a multi-omic single-nucleus study of 191,890 nuclei in late-stage Alzheimer’s disease (AD), accessible through our web portal, profiling chromatin accessibility and gene expression in the same biological samples and uncovering vast cellular heterogeneity. We identified cell-type-specific, disease-associated candidate cis-regulatory elements and their candidate target genes, including an oligodendrocyte-associated regulatory module containing links to APOE and CLU. We describe cis-regulatory relationships in specific cell types at a subset of AD risk loci defined by genome-wide association studies, demonstrating the utility of this multi-omic single-nucleus approach. Trajectory analysis of glial populations identified disease-relevant transcription factors, such as SREBF1, and their regulatory targets. Finally, we introduce single-nucleus consensus weighted gene coexpression analysis, a coexpression network analysis strategy robust to sparse single-cell data, and perform a systems-level analysis of the AD transcriptome.

DOI: 10.1038/s41588-021-00894-z

Source: https://www.nature.com/articles/s41588-021-00894-z

Nature Genetics：《自然—遗传学》，创刊于1992年。隶属于施普林格·自然出版集团，最新IF：41.307
官方网址：https://www.nature.com/ng/
投稿链接：https://mts-ng.nature.com/cgi-bin/main.plex