Molecular Diversity Among Adult Hippocampal and Entorhinal Cells

Franjic, D.; Choi, J.; Skarica, M.; Xu, C.; Li, Q.; Ma, S.; Tebbenkamp, A. T. N.; Santpere, G.; Arellano, J. I.; Gudelj, I.; Jankovic-Rapan, L.; Sousa, A. M. M.; Rakic, P.; Sestan, N.

doi:10.1101/2019.12.31.889139

bioRxiv · 10.1101/2019.12.31.889139

Molecular Diversity Among Adult Hippocampal and Entorhinal Cells

Franjic, D.·Choi, J.·Skarica, M.·Xu, C.·Li, Q.·Ma, S.·Tebbenkamp, A. T. N.·Santpere, G.·Arellano, J. I.·Gudelj, I.·Jankovic-Rapan, L.·Sousa, A. M. M.·Rakic, P.·Sestan, N.

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Abstract

The hippocampal-entorhinal system is comprised of functionally distinct subregions collectively critical for cognition, and selectively vulnerable to aging and pathological processes. To gain insights into neuronal and non-neuronal populations within this system, we performed single-nucleus transcriptional profiling from five human hippocampal-entorhinal subregions. We found that transcriptomic diversity of excitatory neurons across these subregions reflected the molecular transition from three-layered archicortex to six-layered neocortex. Additionally, mRNA and protein for DCX, an immature neuron marker, were clearly detected in some cells, but not in dentate granule cells, the cell-type predicted to be generated in adult neurogenesis. We also found that previously functionally uncharacterized METTL7B was enriched in human and non-human primate neuronal subtypes less vulnerable to initial Alzheimers disease pathology. Proteomic and biochemical assays revealed METTL7B interacts with Alzheimers disease-related proteins, including APP, and its overexpression reduced amyloid-beta generation. These results reveal cell type-specific molecular properties relevant for hippocampal-entorhinal physiology and dysfunction.

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Franjic, D., Choi, J., Skarica, M., Xu, C., Li, Q., Ma, S., Tebbenkamp, A. T. N., Santpere, G., Arellano, J. I., Gudelj, I., Jankovic-Rapan, L., Sousa, A. M. M., Rakic, P., Sestan, N.. 2020-01-02. Molecular Diversity Among Adult Hippocampal and Entorhinal Cells. https://doi.org/10.1101/2019.12.31.889139

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