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Single cell profiling of non-neuronal retinal cells reveals dynamic multicellular responses to central nervous system injury

ABSTRACT: Non-neuronal cells play key roles in the complex cellular interplay that follows central nervous system (CNS) insult. To assess this interplay, we generated single-cell atlases of immune, glial and epithelial cells from adult mouse retina before and at multiple times after axonal transection (optic nerve crush; ONC), delineating changes in their composition, expression, and interactions. After injury, glial reactivation was coupled with chemokine upregulation and a unique retinal pigment epithelial (RPE) cell state. We resolved dynamic trajectories of mononuclear phagocytes, identified resident Ms4a7+MHC-IIhi and Ms4a7+MHC-IIlo subsets, and demonstrated that CCR2+ monocytes give rise to macrophages with overlapping signatures. We documented synchronized multicellular programs and interactions among neurons, glia, RPE and immune cells, highlighting coordinated gliosis, immune activation, and an interferon-response program. Finally, we mapped expression of human retinal disease-related genes by retinal and eyecup cells. Our atlas helps decipher the cellular circuitry, spatial relationships and molecular interactions following CNS injury.

ORGANISM(S): Mus musculus

PROVIDER: GSE199317 | GEO | 2023/02/03

REPOSITORIES: GEO

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