Poo, M. | Search bioRxiv

bioRxiv2025

Multimodal brain cell atlas across the adult macaque lifespan

High-throughput single-cell omics of non-human primate tissues present a remarkable opportunity to study primate brain aging. Here, we introduce a transcriptomic and chromatin accessibility landscape of 1,985,317 cells from eight brain regions of 13 cynomolgus female monkeys spanning adult lifespan including exceptionally old individuals up to 29-years old. This dataset uncovers dynamic molecular changes in critical brain functions such as synaptic communication and axon myelination, exhibiting a high degree of cell type and brain region specificity. We identify the multicellular networks of the pons and medulla as a previously unrecognized hotspot for aging. Furthermore, comparative analyses with human neurodegeneration datasets highlight both shared and distinct mechanisms contributing to aging and disease. In addition, we uncover transcription factors implicated in monkey brain aging and pinpoint aging-regulated loci linked to longevity and neurodegeneration. This spatiotemporal atlas will advance our understanding of primate brain aging and its broader implications for health and disease.

neuroscience↗

bioRxiv2024

Genomic evolution reshapes cell type diversification in the amniote brain

Over 320 million years of evolution, amniotes have developed complex brains and cognition through largely unexplored genetic and gene expression mechanisms. We created a comprehensive single-cell atlas of over 1.3 million cells from the telencephalon and cerebellum of turtles, zebra finches, pigeons, mice, and macaques, employing single-cell resolution spatial transcriptomics to validate gene expression patterns across species. Our study revealed significant species-specific variations in cell types, highlighting their conservation and diversification in evolution. We found pronounced differences in telencephalon excitatory neurons (EX) and cerebellar cell types between birds and mammals. Birds predominantly express SLC17A6 in EX, whereas mammals expressed SLC17A7 in neocortex and SLC17A6 elsewhere, possibly due to loss of SLC17A7 function loss in birds. Additionally, we identified a novel bird-specific Purkinje cell subtype (SVIL+), implicating the LSD11/KDM1A pathway in learning and circadian rhythms, and related numerous positively selected genes in birds, suggesting an evolutionary optimization of cerebellar functions for ecological and behavioral adaptation. Our findings elucidate the complex interplay between genetic evolution and environmental adaptation, underscoring the role of genetic diversification in the development of specialized cell types across amniotes.

evolutionary biology↗