Genetic loss of function of Ptbp1 does not induce glia-to-neuron conversion in retina
Summary: Direct reprogramming of glia into neurons is a potentially promising approach for the replacement of neurons lost to injury or neurodegenerative disorders. Knockdown of the polypyrimidine tract-binding protein Ptbp1 has been recently reported to induce efficient conversion of retinal Mϋller...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-06-01
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| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124722006222 |
| _version_ | 1818231004538601472 |
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| author | Thanh Hoang Dong Won Kim Haley Appel Nicole A. Pannullo Patrick Leavey Manabu Ozawa Sika Zheng Minzhong Yu Neal S. Peachey Seth Blackshaw |
| author_facet | Thanh Hoang Dong Won Kim Haley Appel Nicole A. Pannullo Patrick Leavey Manabu Ozawa Sika Zheng Minzhong Yu Neal S. Peachey Seth Blackshaw |
| author_sort | Thanh Hoang |
| collection | DOAJ |
| description | Summary: Direct reprogramming of glia into neurons is a potentially promising approach for the replacement of neurons lost to injury or neurodegenerative disorders. Knockdown of the polypyrimidine tract-binding protein Ptbp1 has been recently reported to induce efficient conversion of retinal Mϋller glia into functional neurons. Here, we use a combination of genetic lineage tracing, single-cell RNA sequencing (scRNA-seq), and electroretinogram analysis to show that selective induction of either heterozygous or homozygous loss-of-function mutants of Ptbp1 in adult retinal Mϋller glia does not lead to any detectable level of neuronal conversion. Only a few changes in gene expression are observed in Mϋller glia following Ptbp1 deletion, and glial identity is maintained. These findings highlight the importance of using genetic manipulation and lineage-tracing methods in studying cell-type conversion. |
| first_indexed | 2024-12-12T10:43:30Z |
| format | Article |
| id | doaj.art-d7a39380ef884540887e51512ff4db40 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-12T10:43:30Z |
| publishDate | 2022-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-d7a39380ef884540887e51512ff4db402022-12-22T00:26:59ZengElsevierCell Reports2211-12472022-06-013911110849Genetic loss of function of Ptbp1 does not induce glia-to-neuron conversion in retinaThanh Hoang0Dong Won Kim1Haley Appel2Nicole A. Pannullo3Patrick Leavey4Manabu Ozawa5Sika Zheng6Minzhong Yu7Neal S. Peachey8Seth Blackshaw9Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Corresponding authorSolomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Corresponding authorSolomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USASolomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USASolomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USACenter for Experimental Medicine and Systems Biology, University of Tokyo, Tokyo, JapanDivision of Biomedical Sciences, University of California, Riverside, CA, USADepartment of Ophthalmic Research, Cole Eye Institute, Cleveland, OH, USA; Department of Ophthalmology, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH, USADepartment of Ophthalmic Research, Cole Eye Institute, Cleveland, OH, USA; Department of Ophthalmology, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH, USASolomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Kavli Neuroscience Discovery Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Corresponding authorSummary: Direct reprogramming of glia into neurons is a potentially promising approach for the replacement of neurons lost to injury or neurodegenerative disorders. Knockdown of the polypyrimidine tract-binding protein Ptbp1 has been recently reported to induce efficient conversion of retinal Mϋller glia into functional neurons. Here, we use a combination of genetic lineage tracing, single-cell RNA sequencing (scRNA-seq), and electroretinogram analysis to show that selective induction of either heterozygous or homozygous loss-of-function mutants of Ptbp1 in adult retinal Mϋller glia does not lead to any detectable level of neuronal conversion. Only a few changes in gene expression are observed in Mϋller glia following Ptbp1 deletion, and glial identity is maintained. These findings highlight the importance of using genetic manipulation and lineage-tracing methods in studying cell-type conversion.http://www.sciencedirect.com/science/article/pii/S2211124722006222CP: Cell biology |
| spellingShingle | Thanh Hoang Dong Won Kim Haley Appel Nicole A. Pannullo Patrick Leavey Manabu Ozawa Sika Zheng Minzhong Yu Neal S. Peachey Seth Blackshaw Genetic loss of function of Ptbp1 does not induce glia-to-neuron conversion in retina Cell Reports CP: Cell biology |
| title | Genetic loss of function of Ptbp1 does not induce glia-to-neuron conversion in retina |
| title_full | Genetic loss of function of Ptbp1 does not induce glia-to-neuron conversion in retina |
| title_fullStr | Genetic loss of function of Ptbp1 does not induce glia-to-neuron conversion in retina |
| title_full_unstemmed | Genetic loss of function of Ptbp1 does not induce glia-to-neuron conversion in retina |
| title_short | Genetic loss of function of Ptbp1 does not induce glia-to-neuron conversion in retina |
| title_sort | genetic loss of function of ptbp1 does not induce glia to neuron conversion in retina |
| topic | CP: Cell biology |
| url | http://www.sciencedirect.com/science/article/pii/S2211124722006222 |
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