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Updated: Jun 1, 2026
Isolation of Region-specific Microglia from One Adult Mouse Brain Hemisphere for Deep Single-cell RNA Sequencing
Published on: December 3, 2019
Single-Cell RNA Sequencing and Spatial Transcriptomics Reveal a Novel Mechanism of Oligodendrocyte-Neuron Interaction
Wenying Lv1,2, Yuehong Ma2,3, Dongtao Li4
1The Second School of Clinical Medicine, Southern Medical University, Guangzhou, China.
Background:
High-altitude cerebral edema (HACE) leads to cognitive decline, but the underlying cellular and molecular mechanisms remain unclear.
Methods:
We established a mouse model of HACE under hypobaric hypoxia (simulating at an altitude of 6000 m) and analyzed hippocampal changes using single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics (ST) at 3 days and 7 days post-exposure.
Results:
Hypobaric hypoxia induced HACE and cognitive decline by altering the transcriptomic profiles and interactions of oligodendrocytes (MOL and MOL2) and neurons (ExN-L6-CT-2). Early upregulation of PI3K/mTOR in oligodendrocytes mitigated Rps29-bax-mediated ribosomal stress and oxidative phosphorylation, promoting survival and myelin repair. Prolonged hypoxia suppressed PI3K/mTOR, triggering apoptosis/autophagy via oxidative phosphorylation and ribosomal stress. Enhanced Tnfrsf21-App interactions between MOL2 and ExN-L6-CT-2 exacerbated neuroinflammation and cognitive decline.
Conclusions:
Our study reveals that HACE-induced cognitive impairment is closely associated with dysregulated ribosomal stress and oxidative phosphorylation and impaired neuroactive ligand-receptor interactions. Furthermore, we identify PI3K/mTOR dynamics, Rps29-bax-axis, and Tnfrsf21-App as novel regulators, offering potential therapeutic targets.
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