In this article, the authors investigated epigenetic modifications (or chromatin marks) — changes in the 3D packaging of genomic data that affect how genes are expressed — in human immune cells. First, they sought to determine whether different cell types in the immune system tend to display distinct sets of chromatin marks. Next, they addressed the connections between immune chromatin marks and age, examining how chromatin marks change with age and whether this variation has more heritable or environmental influences. They developed a mass cytometry technique called EpiTOF to conduct these complex experiments. The authors’ findings underscore the power of epigenetic analysis to both expand our biological understanding and to address human illnesses.
When exploring epigenetic differences between immune cell types, the authors found that each subtype is characterized by its own set of chromatin marks; furthermore, these changes arise early in cell differentiation, the period when immune cell progenitors diverge to becoming different mature immune cell types. Their findings about which chromatin marks pervade in which cell types provide immunologic insight: for example, mature Memory T cells’ chromatin is more accessible for transcription than naïve T cells, and CD56bright NK cells differentiate along a different hematopoietic lineage than CD56dim NK cells.
In the next section, the authors found that older age is associated with increased epigenetic variability between individuals, as well as between cells within the same individual. Young people have relatively homogenous chromatin modification profiles, but as they age these tend to diversify from others’. In addition, within each individual’s immune system, their cells develop increasingly variable chromatin marks as they age; this single-cell variability is termed epigenetic noise. The authors found that population-level heterogeneity and cell-level noise are related to other age-related signals of genetic and epigenetic deterioration. Then, by comparing groups of identical and fraternal twins the authors discovered that most chromatin mark variance is non-heritable, instead having mostly environmental causes.
The authors conclude that EpiTOF can be used to address epigenetic causes of immune diseases and cancer, and that epigenetic variability between individuals and cells impact transcriptional noise, a well-documented impact of ageing. The authors both expand our knowledge of chromatin marks and purpose potential therapeutic significance while acknowledging that more research is needed before conclusions can be drawn regarding ageing symptoms.
Cheung, P., Vallania, F., Warsinske, H.C., Donato, M., Schaffert, S., Chang, S.E., Dvorak, M., Dekker, C.L., Davis, M.M., Utz, P.J., et al. (2018). Single-Cell Chromatin Modification Profiling Reveals Increased Epigenetic Variations with Aging. Cell 173, 1385-1397.e14.
LINK: https://www.ncbi.nlm.nih.gov/pubmed/29706550
Written By: Zach Altshuler