Institute for Immunity, Transplantation, and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Medicine, Division of Immunology and Rheumatology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Institute for Immunity, Transplantation, and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Medicine, Division of Biomedical Informatics Research, Stanford University School of Medicine, Stanford, CA 94305, USA.
Cell. 2018 May 31;173(6):1385-1397.e14. doi: 10.1016/j.cell.2018.03.079. Epub 2018 Apr 26.
Post-translational modifications of histone proteins and exchanges of histone variants of chromatin are central to the regulation of nearly all DNA-templated biological processes. However, the degree and variability of chromatin modifications in specific human immune cells remain largely unknown. Here, we employ a highly multiplexed mass cytometry analysis to profile the global levels of a broad array of chromatin modifications in primary human immune cells at the single-cell level. Our data reveal markedly different cell-type- and hematopoietic-lineage-specific chromatin modification patterns. Differential analysis between younger and older adults shows that aging is associated with increased heterogeneity between individuals and elevated cell-to-cell variability in chromatin modifications. Analysis of a twin cohort unveils heritability of chromatin modifications and demonstrates that aging-related chromatin alterations are predominantly driven by non-heritable influences. Together, we present a powerful platform for chromatin and immunology research. Our discoveries highlight the profound impacts of aging on chromatin modifications.
组蛋白蛋白的翻译后修饰和染色质组蛋白变体的交换是几乎所有 DNA 模板生物过程调节的核心。然而，特定人类免疫细胞中染色质修饰的程度和可变性在很大程度上仍然未知。在这里，我们采用高度多重化的质谱细胞术分析，在单细胞水平上对多种染色质修饰在原代人类免疫细胞中的整体水平进行了分析。我们的数据揭示了明显不同的细胞类型和造血谱系特异性染色质修饰模式。年轻和老年个体之间的差异分析表明，衰老与个体之间的异质性增加以及染色质修饰的细胞间变异性增加有关。对双胞胎队列的分析揭示了染色质修饰的遗传性，并表明与衰老相关的染色质改变主要由非遗传性影响驱动。总之，我们为染色质和免疫学研究提供了一个强大的平台。我们的发现强调了衰老对染色质修饰的深远影响。
