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Tissue-specific immune transcriptional signatures in the bordering tissues of the mouse brain and retina

ABSTRACT: Bordering the central nervous system (CNS) parenchyma are the pia mater enveloping the brain and the choroid underlying the retina. Although in close proximity to the neural parenchyma, the pia mater and choroid are external to the immune privileged environment of the brain and retina and are distinct immune compartments. This study generated a single cell transcriptomic atlas of immune cells within the healthy adult mouse pia and choroid. Comparative analysis of immune populations within these tissues revealed heterogeneous subtypes of T cells, B cells, monocytes/macrophages and dendritic cells, which displayed tissue-specific transcriptomic signatures and potential functional specialisations. Single cell RNA-sequencing of choroidal immune cells from human eye tissue identified populations with similar transcriptional profiles to mouse choroidal immune cells. This study provides a detailed understanding of the molecular signatures of immune cells within the bordering tissues of the brain and retina, and their potential roles in CNS immune surveillance.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE253419 | GEO | 2024/04/01

REPOSITORIES: GEO

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Project description:The choroid is the vascular layer situated between the outer sclera and the inner retina. Together with the ciliary body and the iris it forms the uvea. Because of its rich blood supply it is also called the nutritive layer and it supplies oxygen and nutrition to the retinal pigment epithelium and the outer retina. Due to its vascular nature it acts as a heat sink and helps in thermoregulation within the eye. It also contains a pigment “melanin”, which absorbs excess light within the eye and prevents scattering. . The human choroid is thickest posteriorly where it measures 0.2 mm, whereas anteriorly it measures 0.1 mm.. The aim of this study was to characterize the choroid proteome to generate a resource for future studies on the choroid . The method used in this study combined bRPLC and LC-MS/MS analysis of the proteins isolated from the three cadaver samples of healthy donors. Subsequently, we classified the proteins based on gene ontology and pathway analysis. A total of 5,249 non redundant proteins were identified in the human choroid. Gene ontology classification pinpointed proteins involved in protein metabolism, regulation of nucleobase, nucleoside, nucleotide and nucleic acid metabolism, transport, cell growth and/or maintenance and immune response. Several proteins identified in normal choroid have previously been identified in human choroid where these proteins are related to glaucoma, ocular inflammation, toxoplasmic retinochoroiditis, diabetic retinopathy, open-angle glaucoma and Grave’s disease. The top canonical pathway in which the choroid proteins participated are EIF2 signaling, integrin signalling, mitochondrial dysfunction, regulation of eIF4 and p70S6K signaling and clathrin-mediated endocytosis signalling. Around 800 choroid proteins were related to infectious diseases. The results of this study illustrate the largest number of proteins identified in human choroid and may serve as a valuable resource for future investigations of choroid biology and disease. Proteomic analysis of choroid proteins could provide versatile information to understand choroidal functions and the underlying pathogenesis of choroidal pathologies.

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Tissue-specific immune transcriptional signatures in the bordering tissues of the mouse brain and retina

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