Translatomic response of retinal Müller glia to acute and chronic stress
Analysis of retina cell type-specific epigenetic and transcriptomic signatures is crucial to understanding the pathophysiology of retinal degenerations such as age-related macular degeneration (AMD) and delineating cell autonomous and cell-non-autonomous mechanisms. We have discovered that Aldh1l1 i...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2022-12-01
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| Series: | Neurobiology of Disease |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996122003230 |
| _version_ | 1811178151276969984 |
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| author | Ana J. Chucair-Elliott Sarah R. Ocañas Kevin Pham Michael Van Der Veldt Ashley Cheyney David Stanford Jami Gurley Michael H. Elliott Willard M. Freeman |
| author_facet | Ana J. Chucair-Elliott Sarah R. Ocañas Kevin Pham Michael Van Der Veldt Ashley Cheyney David Stanford Jami Gurley Michael H. Elliott Willard M. Freeman |
| author_sort | Ana J. Chucair-Elliott |
| collection | DOAJ |
| description | Analysis of retina cell type-specific epigenetic and transcriptomic signatures is crucial to understanding the pathophysiology of retinal degenerations such as age-related macular degeneration (AMD) and delineating cell autonomous and cell-non-autonomous mechanisms. We have discovered that Aldh1l1 is specifically expressed in the major macroglia of the retina, Müller glia, and, unlike the brain, is not expressed in retinal astrocytes. This allows use of Aldh1l1 cre drivers and Nuclear Tagging and Translating Ribosome Affinity Purification (NuTRAP) constructs for temporally controlled labeling and paired analysis of Müller glia epigenomes and translatomes. As validated through a variety of approaches, the Aldh1l1cre/ERT2-NuTRAP model provides Müller glia specific translatomic and epigenomic profiles without the need to isolate whole cells. Application of this approach to models of acute injury (optic nerve crush) and chronic stress (aging) uncovered few common Müller glia-specific transcriptome changes in inflammatory pathways, and mostly differential signatures for each stimulus. The expression of members of the IL-6 and integrin-linked kinase signaling pathways was enhanced in Müller glia in response to optic nerve crush but not aging. Unique changes in neuroinflammation and fibrosis signaling pathways were observed in response to aging but not with optic nerve crush. The Aldh1l1cre/ERT2-NuTRAP model allows focused molecular analyses of a single, minority cell type within the retina, providing more substantial effect sizes than whole tissue analyses. The NuTRAP model, nucleic acid isolation, and validation approaches presented here can be applied to any retina cell type for which a cell type-specific cre is available. |
| first_indexed | 2024-04-11T06:13:29Z |
| format | Article |
| id | doaj.art-d743193742944ce09be1911b654c85e5 |
| institution | Directory Open Access Journal |
| issn | 1095-953X |
| language | English |
| last_indexed | 2024-04-11T06:13:29Z |
| publishDate | 2022-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj.art-d743193742944ce09be1911b654c85e52022-12-22T04:41:08ZengElsevierNeurobiology of Disease1095-953X2022-12-01175105931Translatomic response of retinal Müller glia to acute and chronic stressAna J. Chucair-Elliott0Sarah R. Ocañas1Kevin Pham2Michael Van Der Veldt3Ashley Cheyney4David Stanford5Jami Gurley6Michael H. Elliott7Willard M. Freeman8Genes & Human Disease Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA; Corresponding authors at: Genes & Human Disease Program, Oklahoma Medical Research Foundation, 825 NE 13th Street, Oklahoma City, OK 73104, USA.Genes & Human Disease Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA; Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USAGenes & Human Disease Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USAGenes & Human Disease Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USAGenes & Human Disease Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA; Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USAGenes & Human Disease Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USADepartment of Ophthalmology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USADepartment of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA; Department of Ophthalmology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USAGenes & Human Disease Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA; Oklahoma City Veterans Affairs Medical Center, Oklahoma City, OK, USA; Corresponding authors at: Genes & Human Disease Program, Oklahoma Medical Research Foundation, 825 NE 13th Street, Oklahoma City, OK 73104, USA.Analysis of retina cell type-specific epigenetic and transcriptomic signatures is crucial to understanding the pathophysiology of retinal degenerations such as age-related macular degeneration (AMD) and delineating cell autonomous and cell-non-autonomous mechanisms. We have discovered that Aldh1l1 is specifically expressed in the major macroglia of the retina, Müller glia, and, unlike the brain, is not expressed in retinal astrocytes. This allows use of Aldh1l1 cre drivers and Nuclear Tagging and Translating Ribosome Affinity Purification (NuTRAP) constructs for temporally controlled labeling and paired analysis of Müller glia epigenomes and translatomes. As validated through a variety of approaches, the Aldh1l1cre/ERT2-NuTRAP model provides Müller glia specific translatomic and epigenomic profiles without the need to isolate whole cells. Application of this approach to models of acute injury (optic nerve crush) and chronic stress (aging) uncovered few common Müller glia-specific transcriptome changes in inflammatory pathways, and mostly differential signatures for each stimulus. The expression of members of the IL-6 and integrin-linked kinase signaling pathways was enhanced in Müller glia in response to optic nerve crush but not aging. Unique changes in neuroinflammation and fibrosis signaling pathways were observed in response to aging but not with optic nerve crush. The Aldh1l1cre/ERT2-NuTRAP model allows focused molecular analyses of a single, minority cell type within the retina, providing more substantial effect sizes than whole tissue analyses. The NuTRAP model, nucleic acid isolation, and validation approaches presented here can be applied to any retina cell type for which a cell type-specific cre is available.http://www.sciencedirect.com/science/article/pii/S0969996122003230Müller gliaRetinaTranscriptomeEpigenomeAcute stressOptic nerve crush |
| spellingShingle | Ana J. Chucair-Elliott Sarah R. Ocañas Kevin Pham Michael Van Der Veldt Ashley Cheyney David Stanford Jami Gurley Michael H. Elliott Willard M. Freeman Translatomic response of retinal Müller glia to acute and chronic stress Neurobiology of Disease Müller glia Retina Transcriptome Epigenome Acute stress Optic nerve crush |
| title | Translatomic response of retinal Müller glia to acute and chronic stress |
| title_full | Translatomic response of retinal Müller glia to acute and chronic stress |
| title_fullStr | Translatomic response of retinal Müller glia to acute and chronic stress |
| title_full_unstemmed | Translatomic response of retinal Müller glia to acute and chronic stress |
| title_short | Translatomic response of retinal Müller glia to acute and chronic stress |
| title_sort | translatomic response of retinal muller glia to acute and chronic stress |
| topic | Müller glia Retina Transcriptome Epigenome Acute stress Optic nerve crush |
| url | http://www.sciencedirect.com/science/article/pii/S0969996122003230 |
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