Single-cell transcriptome analyses reveal microglia types associated with proliferative retinopathy
Pathological angiogenesis is a major cause of irreversible blindness in individuals of all age groups with proliferative retinopathy (PR). Mononuclear phagocytes (MPs) within neovascular areas contribute to aberrant retinal angiogenesis. Due to their cellular heterogeneity, defining the roles of MP...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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American Society for Clinical investigation
2022-12-01
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| Series: | JCI Insight |
| Subjects: | |
| Online Access: | https://doi.org/10.1172/jci.insight.160940 |
| _version_ | 1797634393818267648 |
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| author | Zhiping Liu Huidong Shi Jiean Xu Qiuhua Yang Qian Ma Xiaoxiao Mao Zhimin Xu Yaqi Zhou Qingen Da Yongfeng Cai David J.R. Fulton Zheng Dong Akrit Sodhi Ruth B. Caldwell Yuqing Huo |
| author_facet | Zhiping Liu Huidong Shi Jiean Xu Qiuhua Yang Qian Ma Xiaoxiao Mao Zhimin Xu Yaqi Zhou Qingen Da Yongfeng Cai David J.R. Fulton Zheng Dong Akrit Sodhi Ruth B. Caldwell Yuqing Huo |
| author_sort | Zhiping Liu |
| collection | DOAJ |
| description | Pathological angiogenesis is a major cause of irreversible blindness in individuals of all age groups with proliferative retinopathy (PR). Mononuclear phagocytes (MPs) within neovascular areas contribute to aberrant retinal angiogenesis. Due to their cellular heterogeneity, defining the roles of MP subsets in PR onset and progression has been challenging. Here, we aimed to investigate the heterogeneity of microglia associated with neovascularization and to characterize the transcriptional profiles and metabolic pathways of proangiogenic microglia in a mouse model of oxygen-induced PR (OIR). Using transcriptional single-cell sorting, we comprehensively mapped all microglia populations in retinas of room air (RA) and OIR mice. We have unveiled several unique types of PR-associated microglia (PRAM) and identified markers, signaling pathways, and regulons associated with these cells. Among these microglia subpopulations, we found a highly proliferative microglia subset with high self-renewal capacity and a hypermetabolic microglia subset that expresses high levels of activating microglia markers, glycolytic enzymes, and proangiogenic Igf1. IHC staining shows that these PRAM were spatially located within or around neovascular tufts. These unique types of microglia have the potential to promote retinal angiogenesis, which may have important implications for future treatment of PR and other pathological ocular angiogenesis–related diseases. |
| first_indexed | 2024-03-11T12:07:04Z |
| format | Article |
| id | doaj.art-d8faa0a88ffb4375acf7be6ca38fbe1b |
| institution | Directory Open Access Journal |
| issn | 2379-3708 |
| language | English |
| last_indexed | 2024-03-11T12:07:04Z |
| publishDate | 2022-12-01 |
| publisher | American Society for Clinical investigation |
| record_format | Article |
| series | JCI Insight |
| spelling | doaj.art-d8faa0a88ffb4375acf7be6ca38fbe1b2023-11-07T16:24:55ZengAmerican Society for Clinical investigationJCI Insight2379-37082022-12-01723Single-cell transcriptome analyses reveal microglia types associated with proliferative retinopathyZhiping LiuHuidong ShiJiean XuQiuhua YangQian MaXiaoxiao MaoZhimin XuYaqi ZhouQingen DaYongfeng CaiDavid J.R. FultonZheng DongAkrit SodhiRuth B. CaldwellYuqing HuoPathological angiogenesis is a major cause of irreversible blindness in individuals of all age groups with proliferative retinopathy (PR). Mononuclear phagocytes (MPs) within neovascular areas contribute to aberrant retinal angiogenesis. Due to their cellular heterogeneity, defining the roles of MP subsets in PR onset and progression has been challenging. Here, we aimed to investigate the heterogeneity of microglia associated with neovascularization and to characterize the transcriptional profiles and metabolic pathways of proangiogenic microglia in a mouse model of oxygen-induced PR (OIR). Using transcriptional single-cell sorting, we comprehensively mapped all microglia populations in retinas of room air (RA) and OIR mice. We have unveiled several unique types of PR-associated microglia (PRAM) and identified markers, signaling pathways, and regulons associated with these cells. Among these microglia subpopulations, we found a highly proliferative microglia subset with high self-renewal capacity and a hypermetabolic microglia subset that expresses high levels of activating microglia markers, glycolytic enzymes, and proangiogenic Igf1. IHC staining shows that these PRAM were spatially located within or around neovascular tufts. These unique types of microglia have the potential to promote retinal angiogenesis, which may have important implications for future treatment of PR and other pathological ocular angiogenesis–related diseases.https://doi.org/10.1172/jci.insight.160940AngiogenesisOphthalmology |
| spellingShingle | Zhiping Liu Huidong Shi Jiean Xu Qiuhua Yang Qian Ma Xiaoxiao Mao Zhimin Xu Yaqi Zhou Qingen Da Yongfeng Cai David J.R. Fulton Zheng Dong Akrit Sodhi Ruth B. Caldwell Yuqing Huo Single-cell transcriptome analyses reveal microglia types associated with proliferative retinopathy JCI Insight Angiogenesis Ophthalmology |
| title | Single-cell transcriptome analyses reveal microglia types associated with proliferative retinopathy |
| title_full | Single-cell transcriptome analyses reveal microglia types associated with proliferative retinopathy |
| title_fullStr | Single-cell transcriptome analyses reveal microglia types associated with proliferative retinopathy |
| title_full_unstemmed | Single-cell transcriptome analyses reveal microglia types associated with proliferative retinopathy |
| title_short | Single-cell transcriptome analyses reveal microglia types associated with proliferative retinopathy |
| title_sort | single cell transcriptome analyses reveal microglia types associated with proliferative retinopathy |
| topic | Angiogenesis Ophthalmology |
| url | https://doi.org/10.1172/jci.insight.160940 |
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