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Perinatal Brain Injury Triggers Niche-Specific Changes to Cellular Biogeography [MERFISH]

ABSTRACT: Preterm infants are at risk for brain injury and long term neurodevelopmental impairment due, in part, to white matter injury following chronic hypoxia exposure. However, the precise molecular mechanisms by which perinatal hypoxia disrupts early neurodevelopment are poorly understood. Here, we constructed a brain-wide map of the regenerative response to newborn brain injury using high resolution imaging-based spatial transcriptomics (MERFISH) to analyze over 1.3 million cells in a mouse model of chronic neonatal hypoxia. We also developed a new method for inferring condition-associated differences in cell type spatial proximity, enabling the identification of niche-specific changes in cellular architecture. We observed significant hypoxia-associated changes in region-specific cell states, cell type composition, and spatial organization. Our findings suggest that perinatal hypoxia disrupts oligodendrocyte formation and crosstalk signaling with other cell types in their niche. Importantly, our analysis of spatially-informed gene expression patterns revealed specific mechanisms of reparative neurogenesis and gliogenesis, and nominated pathways that may impede circuit rewiring following perinatal hypoxia. Altogether, our work provides a comprehensive description of the brain-wide response to newborn brain injury and identifies candidate signaling pathways for functional interrogation.

ORGANISM(S): Mus musculus synthetic construct

PROVIDER: GSE255892 | GEO | 2024/08/01

REPOSITORIES: GEO

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