A single-nucleus transcriptomic atlas reveals cellular and genetic characteristics in the hippocampus of natural aging-inducing Alzheimer's disease tree shrews
Natural aging-inducing Alzheimer's disease (AD) model is lacking in the current preclinical research. Here, we surprisingly screened 10 tree shrews (TS) with obvious AD phenotypes from 324 naturally aging TS. Using single-nucleus RNA sequencing, we generated the transcriptome atlas of cellular and genetic diversity underlying natural aging-inducing AD development in TS. Further analyses and immunostaining verified the larger proportion of citatory neuronal progenitors exhibiting two different trajectories to an excitatory neuron subtype and granule cells with higher AD relevance. The intensified cellular communication was also found between progenitors and oligodendrocytes. Intriguingly, cross-species analysis among human, TS, monkeys, and mice delineated the cellular heterogeneity and further confirmed higher similarities of TS to monkeys than mice. Overall, our study established the first single-nucleus transcriptomic atlas of hippocampus in a novel AD model, extending our understanding of progenitors in the natural aging processes, and providing striking reference for diagnosis and treatment of AD. Overall design: Nuclei isolated from tissues are re-suspended, filtered and used for 10x channel loading, Using Chromium Next GEM Single Cell 3 ' Reagent Kits v3.1 in Chromium Controller (10 x Genomics) was prepared on mononuclear RNA - seq library.