Single-cell transcriptome reveals diversity of Müller cells with different metabolic-mitochondrial signatures in normal and degenerated macula
Müller cell is the most abundant glial cell in mammalian retina, supporting the functions of photoreceptors and other retinal neurons via maintaining environmental homeostasis. In response to injury and/or neuronal degeneration, Müller cells undergo morphological and functional alternations, known a...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-12-01
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| Series: | Frontiers in Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnins.2022.1079498/full |
| _version_ | 1797979148258377728 |
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| author | Bei Liu Bei Liu Jiali He Ling Zhong Ling Zhong Lulin Huang Lulin Huang Bo Gong Bo Gong Jing Hu Jing Hu Hao Qian Hao Qian Zhenglin Yang Zhenglin Yang Zhenglin Yang |
| author_facet | Bei Liu Bei Liu Jiali He Ling Zhong Ling Zhong Lulin Huang Lulin Huang Bo Gong Bo Gong Jing Hu Jing Hu Hao Qian Hao Qian Zhenglin Yang Zhenglin Yang Zhenglin Yang |
| author_sort | Bei Liu |
| collection | DOAJ |
| description | Müller cell is the most abundant glial cell in mammalian retina, supporting the functions of photoreceptors and other retinal neurons via maintaining environmental homeostasis. In response to injury and/or neuronal degeneration, Müller cells undergo morphological and functional alternations, known as reactive gliosis documented in multiple retinal diseases, including age-related macular degeneration (AMD), retinitis pigmentosa, diabetic retinopathy, and traumatic retinal detachment. But the functional consequences of Müller glia cell reactivation or even the regulatory networks of the retinal gliosis are still controversial. In this study, we reveal different subpopulations of Müller cells with distinct metabolic-mitochondrial signatures by integrating single cell transcriptomic data from Early AMD patients and healthy donors. Our results show that a portion of Müller cells exhibits low mitochondrial DNA (mtDNA) expressions, reduced protein synthesis, impaired homeostatic regulation, decreased proliferative ability but enhanced proangiogenic function. Interestingly, the major alternation of Müller cells in Early AMD retina is the change of subpopulation abundance, rather than generation of new subcluster. Transcription factor enrichment analysis further highlights the key regulators of metabolic-mitochondrial states of Müller glias in Early AMD patients especially. Our study demonstrates new characteristics of retinal gliosis associated with Early AMD and suggests the possibility to prevent degeneration by intervening mitochondrial functions of Müller cells. |
| first_indexed | 2024-04-11T05:35:29Z |
| format | Article |
| id | doaj.art-201d12c5d32b408ea0571dce56eabbf0 |
| institution | Directory Open Access Journal |
| issn | 1662-453X |
| language | English |
| last_indexed | 2024-04-11T05:35:29Z |
| publishDate | 2022-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neuroscience |
| spelling | doaj.art-201d12c5d32b408ea0571dce56eabbf02022-12-22T13:03:50ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2022-12-011610.3389/fnins.2022.10794981079498Single-cell transcriptome reveals diversity of Müller cells with different metabolic-mitochondrial signatures in normal and degenerated maculaBei Liu0Bei Liu1Jiali He2Ling Zhong3Ling Zhong4Lulin Huang5Lulin Huang6Bo Gong7Bo Gong8Jing Hu9Jing Hu10Hao Qian11Hao Qian12Zhenglin Yang13Zhenglin Yang14Zhenglin Yang15Sichuan Provincial Key Laboratory for Human Disease Gene Study, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, ChinaSchool of Medicine, University of Electronic Science and Technology of China, Chengdu, ChinaSchool of Medicine, University of Electronic Science and Technology of China, Chengdu, ChinaSichuan Provincial Key Laboratory for Human Disease Gene Study, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, ChinaResearch Unit for Blindness Prevention of Chinese Academy of Medical Sciences (2019RU026), Sichuan Academy of Medical Sciences, Chengdu, ChinaSichuan Provincial Key Laboratory for Human Disease Gene Study, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, ChinaResearch Unit for Blindness Prevention of Chinese Academy of Medical Sciences (2019RU026), Sichuan Academy of Medical Sciences, Chengdu, ChinaSichuan Provincial Key Laboratory for Human Disease Gene Study, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, ChinaResearch Unit for Blindness Prevention of Chinese Academy of Medical Sciences (2019RU026), Sichuan Academy of Medical Sciences, Chengdu, ChinaSichuan Provincial Key Laboratory for Human Disease Gene Study, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, ChinaSchool of Medicine, University of Electronic Science and Technology of China, Chengdu, ChinaSichuan Provincial Key Laboratory for Human Disease Gene Study, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, ChinaSchool of Medicine, University of Electronic Science and Technology of China, Chengdu, ChinaSichuan Provincial Key Laboratory for Human Disease Gene Study, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, ChinaSchool of Medicine, University of Electronic Science and Technology of China, Chengdu, ChinaResearch Unit for Blindness Prevention of Chinese Academy of Medical Sciences (2019RU026), Sichuan Academy of Medical Sciences, Chengdu, ChinaMüller cell is the most abundant glial cell in mammalian retina, supporting the functions of photoreceptors and other retinal neurons via maintaining environmental homeostasis. In response to injury and/or neuronal degeneration, Müller cells undergo morphological and functional alternations, known as reactive gliosis documented in multiple retinal diseases, including age-related macular degeneration (AMD), retinitis pigmentosa, diabetic retinopathy, and traumatic retinal detachment. But the functional consequences of Müller glia cell reactivation or even the regulatory networks of the retinal gliosis are still controversial. In this study, we reveal different subpopulations of Müller cells with distinct metabolic-mitochondrial signatures by integrating single cell transcriptomic data from Early AMD patients and healthy donors. Our results show that a portion of Müller cells exhibits low mitochondrial DNA (mtDNA) expressions, reduced protein synthesis, impaired homeostatic regulation, decreased proliferative ability but enhanced proangiogenic function. Interestingly, the major alternation of Müller cells in Early AMD retina is the change of subpopulation abundance, rather than generation of new subcluster. Transcription factor enrichment analysis further highlights the key regulators of metabolic-mitochondrial states of Müller glias in Early AMD patients especially. Our study demonstrates new characteristics of retinal gliosis associated with Early AMD and suggests the possibility to prevent degeneration by intervening mitochondrial functions of Müller cells.https://www.frontiersin.org/articles/10.3389/fnins.2022.1079498/fullMüller cellmitochondrial functionage-related macular degenerationgliosismacula |
| spellingShingle | Bei Liu Bei Liu Jiali He Ling Zhong Ling Zhong Lulin Huang Lulin Huang Bo Gong Bo Gong Jing Hu Jing Hu Hao Qian Hao Qian Zhenglin Yang Zhenglin Yang Zhenglin Yang Single-cell transcriptome reveals diversity of Müller cells with different metabolic-mitochondrial signatures in normal and degenerated macula Frontiers in Neuroscience Müller cell mitochondrial function age-related macular degeneration gliosis macula |
| title | Single-cell transcriptome reveals diversity of Müller cells with different metabolic-mitochondrial signatures in normal and degenerated macula |
| title_full | Single-cell transcriptome reveals diversity of Müller cells with different metabolic-mitochondrial signatures in normal and degenerated macula |
| title_fullStr | Single-cell transcriptome reveals diversity of Müller cells with different metabolic-mitochondrial signatures in normal and degenerated macula |
| title_full_unstemmed | Single-cell transcriptome reveals diversity of Müller cells with different metabolic-mitochondrial signatures in normal and degenerated macula |
| title_short | Single-cell transcriptome reveals diversity of Müller cells with different metabolic-mitochondrial signatures in normal and degenerated macula |
| title_sort | single cell transcriptome reveals diversity of muller cells with different metabolic mitochondrial signatures in normal and degenerated macula |
| topic | Müller cell mitochondrial function age-related macular degeneration gliosis macula |
| url | https://www.frontiersin.org/articles/10.3389/fnins.2022.1079498/full |
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