Epigenetic and Transcriptional Heterogeneitytitle

Ageing is accompanied with an increase in epigenetic and transcriptional heterogeneity. This is often seen in bulk experiments, where the individuals cluster apart in simple PCA analysis. Over a decade ago, the first single-cell PCRs also suggested transcriptional heterogeneity from cell to cell, which means that a given gene is expressed to an increasingly variable degree from one cell to another (Vijg lab). While this was an important step towards the understanding of transcriptional heterogeneity, the study was restricted to a few cells and genes. An additional issue in this context is the question whether the composition of tissues changes with age, e.g. through the migration of immune-modulatory cells into a given tissue. We are addressing the question of heterogeneity with age with a specific focus on the interplay between chromatin and transcription at high resolution and are exploiting single-cell approaches, such as scRNA- and scATAC-seq to start elucidating age-dependent heterogeneity on a tissue and cellular level. We combine these approaches with spatial imaging and functional experiments, including more mechanistic experiments in ex vivo systems. In particular, we would use this approach to also increase our understanding of how chromatin and transcription impact each other on a single-cell level.

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