Epigenomic analysis of primary immune cells from young and old animals

National Institute On Aging

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Abstract

Tissue-resident macrophages play a major role in tissue homeostasis. They have also been associated with age-related pathological inflammation. It is important to understand how macrophages are epigenetically and functionally altered during aging and in age-dependent chronic inflammation. To address this question in neuroinflammation, we introduced microglia, the brain-resident macrophages, into human iPSC-derived neural cells in 2D or 3D co-cultures. We also investigated NF-B signaling dynamics, proliferation, and DNA compaction of microglia isolated from young or old mice from our NF-B endogenous knock-in mouse lines. Microglia from old mice had a larger proportion of c-Rel expressing cells and their NF-B signaling was more sustained in response to TNF-alpha. In a collaboration with the Bustin lab, we are investigating the impact of HMGN proteins in gene and chromatin regulation of primary macrophages. This project has been delayed because of the pandemic and hiring issues. We hired a computation scientist contractor and resumed this project in the summer of 2023.