Integrated transcriptomics and epigenomics reveal chamber-specific and species-specific characteristics of human and mouse hearts

作者：Gao, Junpeng; Zheng, Yuxuan; Li, Lin; Lu, Minjie; Chen, Xiangjian; Wang, Yu; Li, Yanna; Liu, Xiaomeng; Gao, Yun; Mao, Yunuo; Zhao, Peng; Zhang, Jinan; Tang, Fuchou; Song, Lei^*; Wen, Lu^*; Wang, Jizheng^*

来源：PLoS Biology, 2021, 19(5): e3001229.

DOI：10.1371/journal.pbio.3001229

• SINGLE-CELL RECONSTRUCTION
• DNA METHYLATION MAPS
• LONG NONCODING RNAS
• GENE-EXPRESSION
• HYPERTROPHIC CARDIOMYOPATHY
• CARDIAC DEVELOPMENT
• OPEN CHROMATIN
• MESSENGER-RNA
• FETAL ORIGINS
• SEQ DATA

DNA methylation, chromatin accessibility, and gene expression represent different levels information in biological process, but a comprehensive multiomics analysis of the mammalian heart is lacking. Here, we applied nucleosome occupancy and methylome sequencing, which detected DNA methylation and chromatin accessibility simultaneously, as well as RNA-seq, for multiomics analysis of the 4 chambers of adult and fetal human hearts, and adult mouse hearts. Our results showed conserved region-specific patterns in the mammalian heart at transcriptome and DNA methylation level. Adult and fetal human hearts showed distinct features in DNA methylome, chromatin accessibility, and transcriptome. Novel long noncoding RNAs were identified in the human heart, and the gene expression profiles of major cardiovascular diseases associated genes were displayed. Furthermore, cross-species comparisons revealed human-specific and mouse-specific differentially expressed genes between the atria and ventricles. We also reported the relationship among multiomics and found there was a bell-shaped relationship between gene-body methylation and expression in the human heart. In general, our study provided comprehensive spatiotemporal and evolutionary insights into the regulation of gene expression in the heart.

• 单位
  南方医科大学; 电子科技大学; 青岛大学; 中国医学科学院北京协和医院; 1; 北京大学