Spatial transcriptomics has drastically transformed our understanding of cellular dynamics in aging and disease by allowing for detailed mapping of molecular and cellular organization across anatomical regions. However, despite these advances, current spatial transcriptomics technologies have limitations in throughput and cost that hinder their application in comprehensive studies. To overcome these limitations, we present IRISeq (Imaging Reconstruction using Indexed Sequencing), a novel and optics-free spatial transcriptomics that removes the requirement of predefined capture arrays or extensive imaging, allowing for rapid and cost-effective processing of several tissue sections simultaneously. IRISeq reconstructs spatial images through the sequencing of local DNA interactions, enabling tissue profiling without constraints on size and at varying resolutions. These local DNA interactions are captured through barcoded receiver beads that capture cellular mRNA and barcoded sender beads with photocleavable linkers. IRISeq was utilized to investigate gene expression and cellular dynamics across thirty brain regions of adult and aged mice in order to elucidate region-specific changes in gene expression associated with aging. Additionally, cell type-focused analysis was conducted to identify age-related cell subtypes and complex changes in cell interactions that are specific to spatial niches in order to elucidate unique region-specific aging processes. These investigations highlight the varied and diverse effects of aging across the brain spatially. The cost-effectiveness, scalability, and simplicity of IRISeq give it the potential to be a versatile tool in mapping region-specific gene expression and cellular interactions across biological systems.
Optics-free Spatial Genomics for Mapping Mouse Brain Aging
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Student Abstract Submission