Friday, April 26, 2024
4/26/2024
PROJECT SUMMARY Brain cells exhibit profound molecular and cellular changes during aging. Epigenomic marks such as DNA methylation are associated with age in multiple human tissues, suggesting an alteration of transcriptional regulation during aging. However, age-associated epigenomic signatures have not been determined with cell- type specificity in the brain. Single-cell epigenomic strategies, such as single-cell DNA methylation and open chromatin profiling assays, are powerful strategies for de novo identification of cell-type specific epigenome landscapes in heterogeneous tissues. At the same time, these strategies uniquely allow the identification of cell- type specific regulatory elements that control gene expression patterns in complex tissues. The proposed project will complement and build upon current NIH-supported BRAIN Initiative efforts to produce an epigenomic cell atlas of the aging mouse brain at the single-cell level. Single-cell DNA methylome and chromatin accessibility data will be generated to allow identification of cell types and cell-type specific regulatory elements in the brains of middle-aged (9 month old) and aged (18 month old) mice, and in brains of aged mice subject to caloric restriction. Aging-associated epigenomic signatures will be identified through comparison to single-cell epigenomic data generated from young mice generated by a BICCN U19 Center for Epigenomics of the Mouse Brain Atlas (CEMBA). Through generation of a comprehensive epigenome-based brain cell reference atlas of the aging mouse brain, the proposed research will provide invaluable resources for the aging-research field.
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