The stability of the myelinating oligodendrocyte transcriptome is regulated by the nuclear lamina
Summary: Oligodendrocytes are specialized cells that insulate and support axons with their myelin membrane, allowing proper brain function. Here, we identify lamin A/C (LMNA/C) as essential for transcriptional and functional stability of myelinating oligodendrocytes. We show that LMNA/C levels incre...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-08-01
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| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124723008598 |
| _version_ | 1797731074910978048 |
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| author | Mathilde Pruvost Julia Patzig Camila Yattah Ipek Selcen Marylens Hernandez Hye-Jin Park Sarah Moyon Shibo Liu Malia S. Morioka Lindsay Shopland Osama Al-Dalahmah Jaroslav Bendl John F. Fullard Panos Roussos James Goldman Ye He Jeffrey L. Dupree Patrizia Casaccia |
| author_facet | Mathilde Pruvost Julia Patzig Camila Yattah Ipek Selcen Marylens Hernandez Hye-Jin Park Sarah Moyon Shibo Liu Malia S. Morioka Lindsay Shopland Osama Al-Dalahmah Jaroslav Bendl John F. Fullard Panos Roussos James Goldman Ye He Jeffrey L. Dupree Patrizia Casaccia |
| author_sort | Mathilde Pruvost |
| collection | DOAJ |
| description | Summary: Oligodendrocytes are specialized cells that insulate and support axons with their myelin membrane, allowing proper brain function. Here, we identify lamin A/C (LMNA/C) as essential for transcriptional and functional stability of myelinating oligodendrocytes. We show that LMNA/C levels increase with differentiation of progenitors and that loss of Lmna in differentiated oligodendrocytes profoundly alters their chromatin accessibility and transcriptional signature. Lmna deletion in myelinating glia is compatible with normal developmental myelination. However, altered chromatin accessibility is detected in fully differentiated oligodendrocytes together with increased expression of progenitor genes and decreased levels of lipid-related transcription factors and inner mitochondrial membrane transcripts. These changes are accompanied by altered brain metabolism, lower levels of myelin-related lipids, and altered mitochondrial structure in oligodendrocytes, thereby resulting in myelin thinning and the development of a progressively worsening motor phenotype. Overall, our data identify LMNA/C as essential for maintaining the transcriptional and functional stability of myelinating oligodendrocytes. |
| first_indexed | 2024-03-12T11:53:17Z |
| format | Article |
| id | doaj.art-3976a992f3b945e0894a415faea3fb6e |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-03-12T11:53:17Z |
| publishDate | 2023-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-3976a992f3b945e0894a415faea3fb6e2023-08-31T05:01:52ZengElsevierCell Reports2211-12472023-08-01428112848The stability of the myelinating oligodendrocyte transcriptome is regulated by the nuclear laminaMathilde Pruvost0Julia Patzig1Camila Yattah2Ipek Selcen3Marylens Hernandez4Hye-Jin Park5Sarah Moyon6Shibo Liu7Malia S. Morioka8Lindsay Shopland9Osama Al-Dalahmah10Jaroslav Bendl11John F. Fullard12Panos Roussos13James Goldman14Ye He15Jeffrey L. Dupree16Patrizia Casaccia17Neuroscience Initiative at the Advanced Science Research Center of the Graduate Center of the City University of New York, 85 St. Nicholas Terrace, New York, NY 10031, USANeuroscience Initiative at the Advanced Science Research Center of the Graduate Center of the City University of New York, 85 St. Nicholas Terrace, New York, NY 10031, USANeuroscience Initiative at the Advanced Science Research Center of the Graduate Center of the City University of New York, 85 St. Nicholas Terrace, New York, NY 10031, USA; Graduate Program in Biochemistry, The Graduate Center of The City University of New York, 365 5th Avenue, New York, NY 10016, USANeuroscience Initiative at the Advanced Science Research Center of the Graduate Center of the City University of New York, 85 St. Nicholas Terrace, New York, NY 10031, USA; Graduate Program in Biochemistry, The Graduate Center of The City University of New York, 365 5th Avenue, New York, NY 10016, USAGraduate School of Biological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USANeuroscience Initiative at the Advanced Science Research Center of the Graduate Center of the City University of New York, 85 St. Nicholas Terrace, New York, NY 10031, USANeuroscience Initiative at the Advanced Science Research Center of the Graduate Center of the City University of New York, 85 St. Nicholas Terrace, New York, NY 10031, USANeuroscience Initiative at the Advanced Science Research Center of the Graduate Center of the City University of New York, 85 St. Nicholas Terrace, New York, NY 10031, USA; Structural Biology Initiative, Advanced Science Research Center at the Graduate Center, City University of New York, New York, NY 10031, USANeuroscience Initiative at the Advanced Science Research Center of the Graduate Center of the City University of New York, 85 St. Nicholas Terrace, New York, NY 10031, USA; Macaulay Honors College, City College of New York, New York, NY 10031, USANeuroscience Initiative at the Advanced Science Research Center of the Graduate Center of the City University of New York, 85 St. Nicholas Terrace, New York, NY 10031, USA; Graduate Program in Biochemistry, The Graduate Center of The City University of New York, 365 5th Avenue, New York, NY 10016, USA; Graduate School of Biological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Structural Biology Initiative, Advanced Science Research Center at the Graduate Center, City University of New York, New York, NY 10031, USA; Macaulay Honors College, City College of New York, New York, NY 10031, USA; Jackson Laboratory, 1650 Santa Ana Ave, Sacramento, CA 95835, USA; Department of Pathology and Cell Biology, Division of Neuropathology, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, and the New York Presbyterian Hospital, New York, NY 10032, USA; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Center for Disease Neurogenomics, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Mental Illness Research, Education, and Clinical Center (VISN 2 South), James J. Peters VA Medical Center, Bronx, NY 10468, USA; Center for Dementia Research, Nathan Kline Institute for Psychiatric Research, Orangeburg, NY 10962, USA; Department of Anatomy and Neurobiology, Virginia Commonwealth University, Richmond, VA 23298, USA; Graduate Program in Biology, The Graduate Center of The City University of New York, 365 5th Avenue, New York, NY 10016, USADepartment of Pathology and Cell Biology, Division of Neuropathology, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, and the New York Presbyterian Hospital, New York, NY 10032, USADepartment of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Center for Disease Neurogenomics, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USADepartment of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Center for Disease Neurogenomics, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USADepartment of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Center for Disease Neurogenomics, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Mental Illness Research, Education, and Clinical Center (VISN 2 South), James J. Peters VA Medical Center, Bronx, NY 10468, USA; Center for Dementia Research, Nathan Kline Institute for Psychiatric Research, Orangeburg, NY 10962, USADepartment of Pathology and Cell Biology, Division of Neuropathology, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, and the New York Presbyterian Hospital, New York, NY 10032, USANeuroscience Initiative at the Advanced Science Research Center of the Graduate Center of the City University of New York, 85 St. Nicholas Terrace, New York, NY 10031, USA; Macaulay Honors College, City College of New York, New York, NY 10031, USADepartment of Anatomy and Neurobiology, Virginia Commonwealth University, Richmond, VA 23298, USANeuroscience Initiative at the Advanced Science Research Center of the Graduate Center of the City University of New York, 85 St. Nicholas Terrace, New York, NY 10031, USA; Graduate Program in Biochemistry, The Graduate Center of The City University of New York, 365 5th Avenue, New York, NY 10016, USA; Graduate School of Biological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Graduate Program in Biology, The Graduate Center of The City University of New York, 365 5th Avenue, New York, NY 10016, USA; Corresponding authorSummary: Oligodendrocytes are specialized cells that insulate and support axons with their myelin membrane, allowing proper brain function. Here, we identify lamin A/C (LMNA/C) as essential for transcriptional and functional stability of myelinating oligodendrocytes. We show that LMNA/C levels increase with differentiation of progenitors and that loss of Lmna in differentiated oligodendrocytes profoundly alters their chromatin accessibility and transcriptional signature. Lmna deletion in myelinating glia is compatible with normal developmental myelination. However, altered chromatin accessibility is detected in fully differentiated oligodendrocytes together with increased expression of progenitor genes and decreased levels of lipid-related transcription factors and inner mitochondrial membrane transcripts. These changes are accompanied by altered brain metabolism, lower levels of myelin-related lipids, and altered mitochondrial structure in oligodendrocytes, thereby resulting in myelin thinning and the development of a progressively worsening motor phenotype. Overall, our data identify LMNA/C as essential for maintaining the transcriptional and functional stability of myelinating oligodendrocytes.http://www.sciencedirect.com/science/article/pii/S2211124723008598CP: Neuroscience |
| spellingShingle | Mathilde Pruvost Julia Patzig Camila Yattah Ipek Selcen Marylens Hernandez Hye-Jin Park Sarah Moyon Shibo Liu Malia S. Morioka Lindsay Shopland Osama Al-Dalahmah Jaroslav Bendl John F. Fullard Panos Roussos James Goldman Ye He Jeffrey L. Dupree Patrizia Casaccia The stability of the myelinating oligodendrocyte transcriptome is regulated by the nuclear lamina Cell Reports CP: Neuroscience |
| title | The stability of the myelinating oligodendrocyte transcriptome is regulated by the nuclear lamina |
| title_full | The stability of the myelinating oligodendrocyte transcriptome is regulated by the nuclear lamina |
| title_fullStr | The stability of the myelinating oligodendrocyte transcriptome is regulated by the nuclear lamina |
| title_full_unstemmed | The stability of the myelinating oligodendrocyte transcriptome is regulated by the nuclear lamina |
| title_short | The stability of the myelinating oligodendrocyte transcriptome is regulated by the nuclear lamina |
| title_sort | stability of the myelinating oligodendrocyte transcriptome is regulated by the nuclear lamina |
| topic | CP: Neuroscience |
| url | http://www.sciencedirect.com/science/article/pii/S2211124723008598 |
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