PT  - JOURNAL ARTICLE
AU  - Daniel Franjic
AU  - Jinmyung Choi
AU  - Mario Skarica
AU  - Chuan Xu
AU  - Qian Li
AU  - Shaojie Ma
AU  - Andrew T. N. Tebbenkamp
AU  - Gabriel Santpere
AU  - Jon I. Arellano
AU  - Ivan Gudelj
AU  - Lucija Jankovic-Rapan
AU  - Andre M. M. Sousa
AU  - Pasko Rakic
AU  - Nenad Sestan
TI  - Molecular Diversity Among Adult Human Hippocampal and Entorhinal Cells
AID  - 10.1101/2019.12.31.889139
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2019.12.31.889139
4099  - http://biorxiv.org/content/early/2020/01/02/2019.12.31.889139.short
4100  - http://biorxiv.org/content/early/2020/01/02/2019.12.31.889139.full
AB  - 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 Alzheimer’s disease pathology. Proteomic and biochemical assays revealed METTL7B interacts with Alzheimer’s 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.