[PDF][PDF] Single-cell chromatin modification profiling reveals increased epigenetic variations with aging

P Cheung, F Vallania, HC Warsinske, M Donato… - Cell, 2018 - cell.com
P Cheung, F Vallania, HC Warsinske, M Donato, S Schaffert, SE Chang, M Dvorak…
Cell, 2018cell.com
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 …
Summary
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.
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