Biology subjects

Feng, M. Y.

Publications and source records attributed to Feng, M. Y..

2 recordsLinked to original sources

bioRxiv2024

Perinatal Brain Injury Triggers Niche-Specific Changes to Cellular Biogeography

Preterm infants are at risk for brain injury and 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 to analyze over 1.3 million cells in a mouse model of chronic neonatal hypoxia. Additionally, we 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 hypoxia-associated changes in region-specific cell states, cell type composition, and spatial organization. Importantly, our analysis revealed mechanisms underlying reparative neurogenesis and gliogenesis, while also nominating pathways that may impede circuit rewiring following perinatal hypoxia. Altogether, our work provides a comprehensive description of the molecular response to newborn brain injury.

neuroscience↗

bioRxiv2023

Single-nucleus profiling identifies accelerated oligodendrocyte precursor cell senescence in a mouse model of Down Syndrome

Down Syndrome (DS), the most common genetic cause of intellectual disability, is associated with lifelong cognitive disability. However, the mechanisms by which triplication of human chromosome 21 genes drive neuroinflammation and cognitive dysfunction are poorly understood. Here, using the Ts65Dn mouse model of DS, we performed an integrated single-nucleus RNA and ATAC-seq analysis of the cortex. We identify cell type-specific transcriptional and chromatin-associated changes in the Ts65Dn cortex, including regulators of neuroinflammation, transcription and translation, myelination, and mitochondrial function. We discover enrichment of a senescence-associated transcriptional signature in Ts65Dn oligodendrocyte precursor cells (OPCs) and epigenetic changes consistent with a loss of heterochromatin. We find that senescence is restricted to a subset of cortical OPCs concentrated in deep cortical layers. Treatment of Ts65Dn mice with a senescence-reducing flavonoid rescues cortical OPC proliferation, restores microglial homeostasis, and improves contextual fear memory. Together, these findings suggest that cortical OPC senescence may be an important driver of neuropathology in DS.

neuroscience↗