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, we expanded our efforts to tissue-resident macrophages including peritoneal, Kupffer, and brain-resident macrophages. We performed ATAC-seq and RNA-seq using tissue-resident macrophages from young and aged mice (NIA aged colony at Charles River Lab) treated with lipopolysaccharide (LPS) for 0, 3, 8 hours. In a recent publication (Babagana M et al. 2021), we characterized the transcriptional changes associated with physiological aging in mouse resident macrophage populations across different tissues and sexes. We found an unexpected role of Hedgehog signaling in modulating the pro-inflammatory cytokine expression in tissue-resident macrophages including microglia and Kupffer cells. The decline of such hedgehog signaling may contribute to the chronically elevated inflammatory signatures associated with aging. 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 put on hold because of the pandemic and hiring freeze. We recently hired a computation scientist contractor and plan to resume this project.