Single-cell RNA sequencing reveals the heterogeneity and interactions of immune cells and Müller glia during zebrafish retina regeneration
Inflammation plays a crucial role in the regeneration of fish and avian retinas. However, how inflammation regulates Müller glia (MG) reprogramming remains unclear. Here, we used single-cell RNA sequencing to investigate the cell heterogeneity and interactions of MG and immune cells in the regenerat...
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| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wolters Kluwer Medknow Publications
2025-12-01
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| Series: | Neural Regeneration Research |
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| Online Access: | https://journals.lww.com/10.4103/NRR.NRR-D-23-02083 |
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| author | Hui Xu Lining Cao Yuxi Chen Cuiping Zhou Jie Xu Zhuolin Zhang Xiangyu Li Lihua Liu Jianfeng Lu |
| author_facet | Hui Xu Lining Cao Yuxi Chen Cuiping Zhou Jie Xu Zhuolin Zhang Xiangyu Li Lihua Liu Jianfeng Lu |
| author_sort | Hui Xu |
| collection | DOAJ |
| description | Inflammation plays a crucial role in the regeneration of fish and avian retinas. However, how inflammation regulates Müller glia (MG) reprogramming remains unclear. Here, we used single-cell RNA sequencing to investigate the cell heterogeneity and interactions of MG and immune cells in the regenerating zebrafish retina. We first showed that two types of quiescent MG (resting MG1 and MG2) reside in the uninjured retina. Following retinal injury, resting MG1 transitioned into an activated state expressing known reprogramming genes, while resting MG2 gave rise to rod progenitors. We further showed that retinal microglia can be categorized into three subtypes (microglia-1, microglia-2, and proliferative) and pseudotime analysis demonstrated dynamic changes in microglial status following retinal injury. Analysis of cell–cell interactions indicated extensive crosstalk between immune cells and MG, with many interactions shared among different immune cell types. Finally, we showed that inflammation activated Jak1–Stat3 signaling in MG, promoting their transition from a resting to an activated state. Our study reveals the cell heterogeneity and crosstalk of immune cells and MG in zebrafish retinal repair, and may provide valuable insights into future mammalian retina regeneration. |
| format | Article |
| id | doaj-art-8e5b1dfc7d1949af86e47575340d60b0 |
| institution | Kabale University |
| issn | 1673-5374 1876-7958 |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Wolters Kluwer Medknow Publications |
| record_format | Article |
| series | Neural Regeneration Research |
| spelling | doaj-art-8e5b1dfc7d1949af86e47575340d60b02025-02-06T09:58:39ZengWolters Kluwer Medknow PublicationsNeural Regeneration Research1673-53741876-79582025-12-0120123635364810.4103/NRR.NRR-D-23-02083Single-cell RNA sequencing reveals the heterogeneity and interactions of immune cells and Müller glia during zebrafish retina regenerationHui XuLining CaoYuxi ChenCuiping ZhouJie XuZhuolin ZhangXiangyu LiLihua LiuJianfeng LuInflammation plays a crucial role in the regeneration of fish and avian retinas. However, how inflammation regulates Müller glia (MG) reprogramming remains unclear. Here, we used single-cell RNA sequencing to investigate the cell heterogeneity and interactions of MG and immune cells in the regenerating zebrafish retina. We first showed that two types of quiescent MG (resting MG1 and MG2) reside in the uninjured retina. Following retinal injury, resting MG1 transitioned into an activated state expressing known reprogramming genes, while resting MG2 gave rise to rod progenitors. We further showed that retinal microglia can be categorized into three subtypes (microglia-1, microglia-2, and proliferative) and pseudotime analysis demonstrated dynamic changes in microglial status following retinal injury. Analysis of cell–cell interactions indicated extensive crosstalk between immune cells and MG, with many interactions shared among different immune cell types. Finally, we showed that inflammation activated Jak1–Stat3 signaling in MG, promoting their transition from a resting to an activated state. Our study reveals the cell heterogeneity and crosstalk of immune cells and MG in zebrafish retinal repair, and may provide valuable insights into future mammalian retina regeneration.https://journals.lww.com/10.4103/NRR.NRR-D-23-02083immune cellsinflammationjak1–stat3 signalingmicrogliamüller gliaregenerationreprogrammingretinasingle-cell rnaseqzebrafish |
| spellingShingle | Hui Xu Lining Cao Yuxi Chen Cuiping Zhou Jie Xu Zhuolin Zhang Xiangyu Li Lihua Liu Jianfeng Lu Single-cell RNA sequencing reveals the heterogeneity and interactions of immune cells and Müller glia during zebrafish retina regeneration Neural Regeneration Research immune cells inflammation jak1–stat3 signaling microglia müller glia regeneration reprogramming retina single-cell rnaseq zebrafish |
| title | Single-cell RNA sequencing reveals the heterogeneity and interactions of immune cells and Müller glia during zebrafish retina regeneration |
| title_full | Single-cell RNA sequencing reveals the heterogeneity and interactions of immune cells and Müller glia during zebrafish retina regeneration |
| title_fullStr | Single-cell RNA sequencing reveals the heterogeneity and interactions of immune cells and Müller glia during zebrafish retina regeneration |
| title_full_unstemmed | Single-cell RNA sequencing reveals the heterogeneity and interactions of immune cells and Müller glia during zebrafish retina regeneration |
| title_short | Single-cell RNA sequencing reveals the heterogeneity and interactions of immune cells and Müller glia during zebrafish retina regeneration |
| title_sort | single cell rna sequencing reveals the heterogeneity and interactions of immune cells and muller glia during zebrafish retina regeneration |
| topic | immune cells inflammation jak1–stat3 signaling microglia müller glia regeneration reprogramming retina single-cell rnaseq zebrafish |
| url | https://journals.lww.com/10.4103/NRR.NRR-D-23-02083 |
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