Transcriptomic characteristics along the longitudinal axis of the hippocampus and medial entorhinal cortex across species
- 1Peking University
Abstract
The hippocampus (HPC) and medial entorhinal cortex (MEC) are essential for learning, memory, and spatial cognition, and both exhibit dorsoventral (longitudinal) organization across mammalian species. While prior studies have highlighted functional differences along this axis, the molecular basis and cross-species conservation of these differences remain poorly understood. Here, we employed spatial transcriptomics to generate a comprehensive molecular atlas of HPC and MEC in five species-human, tree shrew, mouse, canine, and pig-standardizing the dorsoventral axis for cross-species comparison. Using support vector machine (SVM) models, we identified high-weight genes predictive of dorsoventral identity and revealed conserved functional patterns: dorsal HPC was enriched for cytoskeletal and synaptic pathways, while ventral HPC favored nucleotide and energy metabolism. In the MEC, dorsal regions were enriched for calcium transport and lipid metabolism, whereas ventral regions were associated with calcium homeostasis and amyloid regulation. Species-specific SVM models uncovered dramatic divergence, leading us to propose the ancestral confinement theory, suggesting that conserved dorsoventral features are maintained within an evolutionary framework that permits species-specific adaptations. To link molecular patterns with cell types, we conducted single-nucleus RNA sequencing of tree shrew HPC and MEC and integrated data from other species. Deconvolution analysis showed species-specific GABAergic neuron distributions along the axis, with notable dorsal enrichment in human and ventral enrichment in other species. Together, our findings provide a cross-species molecular framework of HPC and MEC organization, revealing both conserved and species-specific dorsoventral programs underlying brain function and evolution.
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BibTeX
@misc{cheng2026transcriptomic,
title = {{Transcriptomic characteristics along the longitudinal axis of the hippocampus and medial entorhinal cortex across species}},
author = {S. Cheng and Q. Wang and Y. Feng and C. Chen and G. Suri and Y. Liang and Y. Yang and K. Gao and M. Witter and H. Yang and J. Lin and C. Miao},
howpublished = {bioRxiv},
year = {2026},
month = aug,
doi = {10.64898/2026.08.26.746438},
url = {https://www.biorxiv.org/content/10.64898/2026.08.26.746438v1},
note = {CC BY-NC},
}
RIS
TY - UNPB
TI - Transcriptomic characteristics along the longitudinal axis of the hippocampus and medial entorhinal cortex across species
AU - S. Cheng
AU - Q. Wang
AU - Y. Feng
AU - C. Chen
AU - G. Suri
AU - Y. Liang
AU - Y. Yang
AU - K. Gao
AU - M. Witter
AU - H. Yang
AU - J. Lin
AU - C. Miao
PY - 2026
DA - 2026/08/26
PB - bioRxiv
DO - 10.64898/2026.08.26.746438
UR - https://www.biorxiv.org/content/10.64898/2026.08.26.746438v1
AB - The hippocampus (HPC) and medial entorhinal cortex (MEC) are essential for learning, memory, and spatial cognition, and both exhibit dorsoventral (longitudinal) organization across mammalian species. While prior studies have highlighted functional differences along this axis, the molecular basis and cross-species conservation of these differences remain poorly understood. Here, we employed spatial transcriptomics to generate a comprehensive molecular atlas of HPC and MEC in five species-human, tree shrew, mouse, canine, and pig-standardizing the dorsoventral axis for cross-species comparison. Using support vector machine (SVM) models, we identified high-weight genes predictive of dorsoventral identity and revealed conserved functional patterns: dorsal HPC was enriched for cytoskeletal and synaptic pathways, while ventral HPC favored nucleotide and energy metabolism. In the MEC, dorsal regions were enriched for calcium transport and lipid metabolism, whereas ventral regions were associated with calcium homeostasis and amyloid regulation. Species-specific SVM models uncovered dramatic divergence, leading us to propose the ancestral confinement theory, suggesting that conserved dorsoventral features are maintained within an evolutionary framework that permits species-specific adaptations. To link molecular patterns with cell types, we conducted single-nucleus RNA sequencing of tree shrew HPC and MEC and integrated data from other species. Deconvolution analysis showed species-specific GABAergic neuron distributions along the axis, with notable dorsal enrichment in human and ventral enrichment in other species. Together, our findings provide a cross-species molecular framework of HPC and MEC organization, revealing both conserved and species-specific dorsoventral programs underlying brain function and evolution.
ER -