Epigenomic analysis of primary immune cells from young and old animals

National Institute On Aging

Investigators

Linked publications & trials

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 explored various methods of introducing microglia, the brain-resident macrophages, into human iPSC-derived 3D neural organoid cultures. We compare different methods such as injection of microglia to 3D cultures, addition to cultures, and 2D 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 put on hold because of the pandemic and difficulty in hiring. We will hire a computation scientist contractor and plan to resume this project.