A Single-Cell Transcriptome Atlas of Glia Diversity in the Human Hippocampus across the Lifespan and in Alzheimer’s Disease

Hippocampus is a critical region involved in learning, memory and various brain disorders. The molecular diversity of various glial cells in the human hippocampus and their temporal changes over the postnatal life remain largely unknown. Here we performed single-nucleus RNA-sequencing to create a transcriptome atlas of the human hippocampus across the postnatal lifespan and in Alzheimer’s disease (AD). Detailed analyses of astrocytes, oligodendrocyte lineages, and microglia identified subpopulations with distinct transcriptomic signatures, transcription factor expression patterns, association with specific biological processes, and changes in their abundance with age. Enrichment analysis of brain disorder risk gene expression further implicates specific glial cells and subpopulations in various brain disorders. Furthermore, we identified dysregulated gene expression in specific glial subpopulations in the hippocampus of AD patients. Together, these data provide a rich resource and significantly extend our understanding of human glial cell diversity and their temporal distribution across the postnatal lifespan. Overall design: single nucleus RNA-seq on human hippocampus

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