NCM 2022: Direct RNA sequencing of mouse brain samples from the RIKEN aging project
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The RIKEN Ageing Project is a multi-center and multi-disciplinary project that looks to provide a detailed account of genetic, transcriptomic, metabolic and phenotypic changes of the model mouse during aging. With a particular focus inflammaging, the study of how inflammatory insults during life can drive overall health of an individual during the aging process. On single-cell analysis of immune cells throughout multiple organs, and the influence microbiota by comparing standard specific-pathogen-free (SPF) housing versus specially reared germ-free (GF) mice. Alternative splicing of RNA allows for a greater number of RNA isoforms and protein variants to be expressed from the same genome and involved in cell specification during development. However, little is known of how dynamic the expression at the isoform level is within a cell type during the ageing process of humans. The brain is resident to the oldest cells in our body, and therefore provides a history of ageing at the molecular level. Due to the complexity of splicing in the brain, we will leverage long-read direct RNA Nanopore sequencing to overcome current sequencing limitations. We will map the dynamic nature of RNA splicing of brain cell types and states of the brain. We envisage discovering linked isoforms and RNA modifications to the ageing process and age-associated diseases, such as Alzheimer’s disease. Overall, the gene changes during aging differ between animals housed in standard specific-pathogen free housing and those in germ-free environment.