Single-cell epigenome analysis reveals age-associated decay of heterochromatin domains in excitatory neurons in the mouse brain  

作　　者：Yanxiao Zhang Maria Luisa Amaral Chenxu Zhu Steven Francis Grieco Xiaomeng Hou Lin Lin Justin Buchanan Liqi Tong Sebastian Preissl Xiangmin Xu Bing Ren 

机构地区：[1]Ludwig Institute for Cancer Research,La Jolla,CA,USA [2]School of Life Sciences,Westlake University,Hangzhou,China [3]Bioinformatics and Systems Biology Graduate Program,University of California San Diego,La Jolla,CA,USA [4]Department of Anatomy and Neurobiology,School of Medicine,University of California,Irvine,CA,USA [5]Center for Epigenomics,University of California San Diego,La Jolla,CA,USA [6]Institute of Experimental and Clinical Pharmacology and Toxicology,Faculty of Medicine,University of Freiburg,Freiburg,Germany [7]The Center for Neural Circuit Mapping,University of California,Irvine,CA,USA [8]Department of Cellular and Molecular Medicine,University of California San Diego School of Medicine,La Jolla,CA,USA [9]Institute for Genomic Medicine,University of California San Diego,La Jolla,CA,USA

出　　处：《Cell Research》2022年第11期1008-1021,共14页细胞研究（英文版）

基　　金：supported by funding from Ludwig Institute for Cancer Research(to B.R.);NIH grants 1R01AG067153(to X.X,B.R.),R01AG066018(to B.R.);supported in part by NIH K99CA252020;supported by an NIH training grant(T32GM008806-18);in part by NIH K99HG011483.

摘　　要：Loss of heterochromatin has been implicated as a cause of pre-mature aging and age-associated decline in organ functions in mammals;however,the specific cell types and gene loci affected by this type of epigenetic change have remained unclear.To address this knowledge gap,we probed chromatin accessibility at single-cell resolution in the brains,hearts,skeletal muscles,and bone marrows from young,middle-aged,and old mice,and assessed age-associated changes at 353,126 candidate cis-regulatory elements(cCREs)across 32 major cell types.Unexpectedly,we detected increased chromatin accessibility within specific heterochromatin domains in old mouse excitatory neurons.The gain of chromatin accessibility at these genomic loci was accompanied by the cell-type-specific loss of heterochromatin and activation of LINE1 elements.Immunostaining further confirmed the loss of the heterochromatin mark H3K9me3 in the excitatory neurons but not in inhibitory neurons or glial cells.Our results reveal the cell-type-specific changes in chromatin landscapes in old mice and shed light on the scope of heterochromatin loss in mammalian aging.

关 键 词：EXCITATORY assessed CHROMATIN 

分 类 号：R392.2[医药卫生—免疫学]