A DNA methylation atlas of normal human cell types.
A DNA methylation atlas of normal human cell types.
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DOI：
10.1038/s41586-022-05580-6
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发表时间：
2023-01
期刊：
影响因子：
64.8
通讯作者：
Kaplan, Tommy
中科院分区：
文献类型：
--
作者：
Loyfer, Netanel;Magenheim, Judith;Peretz, Ayelet;Cann, Gordon;Bredno, Joerg;Klochendler, Agnes;Fox-Fisher, Ilana;Shabi-Porat, Sapir;Hecht, Merav;Pelet, Tsuria;Moss, Joshua;Drawshy, Zeina;Amini, Hamed;Moradi, Patriss;Nagaraju, Sudharani;Bauman, Dvora;Shveiky, David;Porat, Shay;Dior, Uri;Rivkin, Gurion;Or, Omer;Hirshoren, Nir;Carmon, Einat;Pikarsky, Alon;Khalaileh, Abed;Zamir, Gideon;Grinbaum, Ronit;Abu Gazala, Machmud;Mizrahi, Ido;Shussman, Noam;Korach, Amit;Wald, Ori;Izhar, Uzi;Erez, Eldad;Yutkin, Vladimir;Samet, Yaacov;Rotnemer Golinkin, Devorah;Spalding, Kirsty L.;Druid, Henrik;Arner, Peter;Shapiro, A. M. James;Grompe, Markus;Aravanis, Alex;Venn, Oliver;Jamshidi, Arash;Shemer, Ruth;Dor, Yuval;Glaser, Benjamin;Kaplan, Tommy
DNA甲基化是控制基因表达和染色质组织的基本表观遗传标记，因此为细胞身份和发育过程提供了一个窗口。目前的数据集通常只包括一小部分甲基化位点，并且通常是基于在培养过程中发生巨大变化的细胞系或包含未指定的细胞混合物的组织。在这里，我们描述了一个基于深度全基因组亚硫酸盐测序的人类甲基组图谱，允许对来自205个健康组织样本的39种细胞类型的数千种独特标记进行片段水平分析。相同细胞类型的复制超过99.5%相同，证明细胞身份程序对环境扰动的鲁棒性。图谱的无监督聚类概括了组织个体发生的关键要素，并确定了自胚胎发育以来保留的甲基化模式。单个细胞类型中唯一未甲基化的基因座通常位于转录增强子中，并包含组织特异性转录调节因子的DNA结合位点。独特的高甲基化位点是罕见的，并且在CpG岛，Polycomb靶点和CTCF结合位点上富集，这表明在形成细胞类型特异性染色质环中具有新的作用。该图谱为基因调控和疾病相关遗传变异的研究提供了重要资源，并为液体活检提供了大量潜在的组织特异性生物标志物。我们描述了基于深度全基因组亚硫酸盐测序的人类DNA甲基组图谱，允许对细胞类型特异性标记进行片段水平分析，并为基因调控研究、细胞混合物反褶积和液体活检提供重要资源。
DNA methylation is a fundamental epigenetic mark that governs gene expression and chromatin organization, thus providing a window into cellular identity and developmental processes. Current datasets typically include only a fraction of methylation sites and are often based either on cell lines that underwent massive changes in culture or on tissues containing unspecified mixtures of cells. Here we describe a human methylome atlas, based on deep whole-genome bisulfite sequencing, allowing fragment-level analysis across thousands of unique markers for 39 cell types sorted from 205 healthy tissue samples. Replicates of the same cell type are more than 99.5% identical, demonstrating the robustness of cell identity programmes to environmental perturbation. Unsupervised clustering of the atlas recapitulates key elements of tissue ontogeny and identifies methylation patterns retained since embryonic development. Loci uniquely unmethylated in an individual cell type often reside in transcriptional enhancers and contain DNA binding sites for tissue-specific transcriptional regulators. Uniquely hypermethylated loci are rare and are enriched for CpG islands, Polycomb targets and CTCF binding sites, suggesting a new role in shaping cell-type-specific chromatin looping. The atlas provides an essential resource for study of gene regulation and disease-associated genetic variants, and a wealth of potential tissue-specific biomarkers for use in liquid biopsies. We describe a human DNA methylome atlas based on deep whole-genome bisulfite sequencing, allowing fragment-level analysis of cell-type-specific markers and providing an essential resource for studies of gene regulation and for deconvolution of cell mixtures and liquid biopsies.
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影响因子：
4.4
作者：
Bibikova, Marina;Barnes, Bret;Shen, Richard
通讯作者：
Shen, Richard
遗传对人体组织基因表达的影响。
影响因子：
64.8
作者：
GTEx Consortium;Laboratory, Data Analysis &Coordinating Center (LDACC)—Analysis Working Group;Statistical Methods groups—Analysis Working Group;Enhancing GTEx (eGTEx) groups;NIH Common Fund;NIH/NCI;NIH/NHGRI;NIH/NIMH;NIH/NIDA;Biospecimen Collection Source Site—NDRI;Biospecimen Collection Source Site—RPCI;Biospecimen Core Resource—VARI;Brain Bank Repository—University of Miami Brain Endowment Bank;Leidos Biomedical—Project Management;ELSI Study;Genome Browser Data Integration &Visualization—EBI;Genome Browser Data Integration &Visualization—UCSC Genomics Institute, University of California Santa Cruz;Lead analysts:;Laboratory, Data Analysis &Coordinating Center (LDACC):;NIH program management:;Biospecimen collection:;Pathology:;eQTL manuscript working group:;Battle A;Brown CD;Engelhardt BE;Montgomery SB
通讯作者：
Montgomery SB
全基因组甲基化谱揭示了人类衰老速度的定量观点。
影响因子：
16
作者：
Hannum, Gregory;Guinney, Justin;Zhao, Ling;Zhang, Li;Hughes, Guy;Sadda, SriniVas;Klotzle, Brandy;Bibikova, Marina;Fan, Jian-Bing;Gao, Yuan;Deconde, Rob;Chen, Menzies;Rajapakse, Indika;Friend, Stephen;Ideker, Trey;Zhang, Kang
通讯作者：
Zhang, Kang
影响因子：
14.9
作者：
Li W;Li Q;Kang S;Same M;Zhou Y;Sun C;Liu CC;Matsuoka L;Sher L;Wong WH;Alber F;Zhou XJ
通讯作者：
Zhou XJ
影响因子：
5.9
作者：
Franzen J;Georgomanolis T;Selich A;Kuo CC;Stöger R;Brant L;Mulabdić MS;Fernandez-Rebollo E;Grezella C;Ostrowska A;Begemann M;Nikolić M;Rath B;Ho AD;Rothe M;Schambach A;Papantonis A;Wagner W
通讯作者：
Wagner W