TY - JOUR
T1 - Single-cell transcriptome analyses reveal microglia types associated with proliferative retinopathy
AU - Liu, Zhiping
AU - Shi, Huidong
AU - Xu, Jiean
AU - Yang, Qiuhua
AU - Ma, Qian
AU - Mao, Xiaoxiao
AU - Xu, Zhimin
AU - Zhou, Yaqi
AU - Da, Qingen
AU - Cai, Yongfeng
AU - Fulton, David J.R.
AU - Dong, Zheng
AU - Sodhi, Akrit
AU - Caldwell, Ruth B.
AU - Huo, Yuqing
N1 - Publisher Copyright:
© 2022, Liu et al. This is an open access article published under the terms of the Creative Commons Attribution 4.0 International License.
PY - 2022/12/8
Y1 - 2022/12/8
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/85143513047
U2 - 10.1172/jci.insight.160940
DO - 10.1172/jci.insight.160940
M3 - Article
C2 - 36264636
AN - SCOPUS:85143513047
SN - 2379-3708
VL - 7
JO - JCI Insight
JF - JCI Insight
IS - 23
M1 - e160940
ER -