Spatially-resolved transcriptomics of human dentate gyrus across postnatal lifespan reveals heterogeneity in markers for proliferation, extracellular matrix, and neuroinflammation

Ramnauth, A. D.; Tippani, M.; Divecha, H. R.; Papariello, A. R.; Miller, R. A.; Pattie, E. A.; Kleinman, J. E.; Maynard, K. R.; Collado-Torres, L.; Hyde, T. M.; Martinowich, K.; Hicks, S. C.; Page, S. C.

doi:10.1101/2023.11.20.567883

bioRxiv · 10.1101/2023.11.20.567883

Spatially-resolved transcriptomics of human dentate gyrus across postnatal lifespan reveals heterogeneity in markers for proliferation, extracellular matrix, and neuroinflammation

Ramnauth, A. D.·Tippani, M.·Divecha, H. R.·Papariello, A. R.·Miller, R. A.·Pattie, E. A.·Kleinman, J. E.·Maynard, K. R.·Collado-Torres, L.·Hyde, T. M.·Martinowich, K.·Hicks, S. C.·Page, S. C.

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Abstract

The dentate gyrus of the hippocampus is important for many cognitive functions, including learning, memory, and mood. Here, we investigated age-associated changes in transcriptome-wide spatial gene expression in the human dentate gyrus across the lifespan. Genes associated with neurogenesis and the extracellular matrix were enriched in infants, while gene markers of inhibitory neurons and cell proliferation showed increases and decreases in post-infancy, respectively. While we did not find evidence for neural proliferation post-infancy, we did identify molecular signatures supporting protracted maturation of granule cells. We also identified a wide-spread hippocampal aging signature and an age-associated increase in genes related to neuroinflammation. Our findings suggest major changes to the putative neurogenic niche after infancy and identify molecular foci of brain aging in glial and neuropil enriched tissue.

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Ramnauth, A. D., Tippani, M., Divecha, H. R., Papariello, A. R., Miller, R. A., Pattie, E. A., Kleinman, J. E., Maynard, K. R., Collado-Torres, L., Hyde, T. M., Martinowich, K., Hicks, S. C., Page, S. C.. 2023-11-21. Spatially-resolved transcriptomics of human dentate gyrus across postnatal lifespan reveals heterogeneity in markers for proliferation, extracellular matrix, and neuroinflammation. https://doi.org/10.1101/2023.11.20.567883

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