Comprehensive analysis of a mouse model of spontaneous uveoretinitis using single-cell RNA sequencing
Comprehensive analysis of a mouse model of spontaneous uveoretinitis using single-cell RNA sequencing
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DOI：
10.1073/pnas.1915571116
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发表时间：
2019-12-26
影响因子：
11.1
通讯作者：
Nathans, Jeremy
中科院分区：
文献类型：
--
作者：
Heng, Jacob S.;Hackett, Sean F.;Nathans, Jeremy
Autoimmune uveoretinitis is a significant cause of visual loss, and mouse models offer unique opportunities to study its disease mechanisms. Aire(-/-) mice fail to express self-antigens in the thymus, exhibit reduced central tolerance, and develop a spontaneous, chronic, and progressive uveoretinitis. Using single-cell RNA sequencing (scRNA-seq), we characterized wild-type and Aire(-/-) retinas to define, in a comprehensive and unbiased manner, the cell populations and gene expression patterns associated with disease. Based on scRNA-seq, immunostaining, and in situ hybridization, we infer that 1) the dominant effector response in Aire(-/-) retinas is Th1-driven, 2) a subset of monocytes convert to either a macrophage/microglia state or a dendritic cell state, 3) the development of tertiary lymphoid structures constitutes part of the Aire(-/-) retinal phenotype, 4) all major resident retinal cell types respond to interferon gamma (IFNG) by changing their patterns of gene expression, and 5) Muller glia up-regulate specific genes in response to IFN gamma and may act as antigen-presenting cells.
