RT Journal Article
SR Electronic
T1 Molecular Diversity Among Adult Human Hippocampal and Entorhinal Cells
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2019.12.31.889139
DO 10.1101/2019.12.31.889139
A1 Daniel Franjic
A1 Jinmyung Choi
A1 Mario Skarica
A1 Chuan Xu
A1 Qian Li
A1 Shaojie Ma
A1 Andrew T. N. Tebbenkamp
A1 Gabriel Santpere
A1 Jon I. Arellano
A1 Ivan Gudelj
A1 Lucija Jankovic-Rapan
A1 Andre M. M. Sousa
A1 Pasko Rakic
A1 Nenad Sestan
YR 2020
UL http://biorxiv.org/content/early/2020/01/02/2019.12.31.889139.abstract
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.