Genome-wide Analysis of Differential Transcriptional and Epigenetic Variability Across Human Immune Cell Types

Abstract

Background: A healthy immune system requires immune cells that adapt rapidly to environmental challenges. This phenotypic plasticity can be mediated by transcriptional and epigenetic variability. Results: We apply a novel analytical approach to measure and compare transcriptional and epigenetic variability genome-wide across CD14

Epigenetic and Transcriptional Variability Shape Phenotypic Plasticity

“…The relative contributions of different sources of variability can be different in distinct cell types, and are only starting to be revealed. For example, DNA methylation variability of T cells was found to be associated with donor age at many loci, while in monocytes, DNA methylation variability associated more often with season . Interestingly, we found more than a thousand genes with small but significant sex‐specific differential expression in neutrophils, while monocytes and T cells showed less sex‐specific gene expression .…”

“…For example, DNA methylation variability of T cells was found to be associated with donor age at many loci, while in monocytes, DNA methylation variability associated more often with season . Interestingly, we found more than a thousand genes with small but significant sex‐specific differential expression in neutrophils, while monocytes and T cells showed less sex‐specific gene expression . Thus, variability can be different for the same gene across cell types and distinct tissues, and can be influenced by distinct factors.…”

Interindividual epigenetic variability: Sound or noise?

“…The work of Ecker et al [11], as well as other studies mentioned above, constitutes a significant advance in our understanding of the causes -and possibly the consequences -of molecular variability in complex biological scenarios, such as the immune system response, the aging process and cancer. The work of Ecker et al [11], as well as other studies mentioned above, constitutes a significant advance in our understanding of the causes -and possibly the consequences -of molecular variability in complex biological scenarios, such as the immune system response, the aging process and cancer.…”

“…A recent report by Ecker and co-workers has unraveled, in a genome-wide manner, the extent of transcriptional and epigenetic variability in three major immune cell types [11]. Taking advantage of the publicly available BLUEPRINT Human Variation Panel, the authors analyzed RNA-seq and array-based DNA methylation data from 125 donors using transcriptomic and epigenomic datasets matched across…”

“…While a clear consensus has not yet been established as regards the concept of epigenetic drift, the accumulation of DNA methylation noise over time might result in changes with direct or indirect biological effects [23,52]. Moreover, age-related epigenetic changes seem to alter the functional capacity of T cells [11,54], but not other immune cell types [11], and thus increased epigenetic variability in the adaptive immune system and the subsequent dysregulation of genes related to T-cell differentiation [54] might have a more severe impact in reduced responsiveness to infections during aging. As this effect seems to be a gradual, rather than a programmed phenomenon, it argues against the hypothesis of an age-related decline in writers or editors of DNA methylation.…”