索尔克生物研究所Joseph R. Ecker团队取得一项新突破。他们的最新研究揭示了遗传和环境独特地塑造了人类免疫细胞的表观基因组。相关论文于2026年1月27日发表在《自然—遗传学》杂志上。

在这里，该研究团队以单核甲基化测序和转座酶可及染色质主题测序（ATAC-seq）为主题，系统地探索病原体和化学暴露以及遗传变异如何与免疫细胞表观基因组的变化相关。鉴定出不同暴露相关的差异甲基化区域（eDMRs）和差异可及区域，并观察到这两种模式之间的显著相关性。此外，检测到基因型相关的DMRs (gDMRs)，表明eDMRs富集于调控区域，而gDMRs优先位于基因体标记内。疾病相关的单核苷酸多态性经常与甲基化数量性状位点共定位，为疾病的遗传基础提供了细胞类型特异性的见解。这些发现强调了形成免疫细胞表观基因组的遗传和环境因素之间复杂的相互作用，并促进了对免疫细胞在健康和疾病中的调节的理解。

据悉，人类免疫细胞的表观基因组是由遗传和环境因素共同塑造的，但这些影响的相对贡献仍然不完全表征。

附：英文原文

Title: Genetics and environment distinctively shape the human immune cell epigenome

Author: Wang, Wenliang, Hariharan, Manoj, Ding, Wubin, Bartlett, Anna, Barragan, Cesar, Castanon, Rosa, Wang, Ruoxuan, Rothenberg, Vince, Song, Haili, Nery, Joseph R., Aldridge, Andrew, Altshul, Jordan, Kenworthy, Mia, Liu, Hanqing, Tian, Wei, Zhou, Jingtian, Zeng, Qiurui, Chen, Huaming, Wei, Bei, Gndz, Irem B., Norell, Todd, Broderick, Timothy J., McClain, Micah T., Satterwhite, Lisa L., Burke, Thomas W., Petzold, Elizabeth A., Shen, Xiling, Woods, Christopher W., Fowler, Vance G., Ruffin, Felicia, Panuwet, Parinya, Barr, Dana B., Beare, Jennifer L., Smith, Anthony K., Spurbeck, Rachel R., Vangeti, Sindhu, Ramos, Irene, Nudelman, German, Sealfon, Stuart C., Castellino, Flora, Walley, Anna Maria, Evans, Thomas, Mller, Fabian, Greenleaf, William J., Ecker, Joseph R.

Issue&Volume: 2026-01-27

Abstract: The epigenome of human immune cells is shaped by both genetics and environmental factors, yet the relative contributions of these influences remain incompletely characterized. Here we use single-nucleus methylation sequencing and assay for transposase-accessible chromatin using sequencing (ATAC–seq) to systematically explore how pathogen and chemical exposures, along with genetic variation, are associated with changes in the immune cell epigenome. Distinct exposure-associated differentially methylated regions (eDMRs) and differentially accessible regions were identified, and a significant correlation between these two modalities was observed. Additionally, genotype-associated DMRs (gDMRs) were detected, indicating that eDMRs are enriched in regulatory regions, whereas gDMRs are preferentially located within gene body marks. Disease-associated single-nucleotide polymorphisms were frequently colocalized with methylation quantitative trait loci, providing cell-type-specific insights into the genetic basis of diseases. These findings highlight the complex interplay between genetic and environmental factors in shaping the immune cell epigenome and advance understanding of immune cell regulation in health and disease.

DOI: 10.1038/s41588-025-02479-6

Source: https://www.nature.com/articles/s41588-025-02479-6