Cell Reports (Aug 2023)
The stability of the myelinating oligodendrocyte transcriptome is regulated by the nuclear lamina
- 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
Affiliations
- Mathilde Pruvost
- Neuroscience 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
- Julia Patzig
- Neuroscience 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
- Camila Yattah
- Neuroscience 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
- Ipek Selcen
- Neuroscience 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
- Marylens Hernandez
- Graduate School of Biological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
- Hye-Jin Park
- Neuroscience 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
- Sarah Moyon
- Neuroscience 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
- Shibo Liu
- Neuroscience 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, USA
- Malia S. Morioka
- Neuroscience 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, USA
- Lindsay Shopland
- Neuroscience 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, USA
- Osama Al-Dalahmah
- 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
- Jaroslav Bendl
- 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
- John F. Fullard
- 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
- Panos Roussos
- 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
- James Goldman
- 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
- Ye He
- Neuroscience 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, USA
- Jeffrey L. Dupree
- Department of Anatomy and Neurobiology, Virginia Commonwealth University, Richmond, VA 23298, USA
- Patrizia Casaccia
- Neuroscience 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 author
- Journal volume & issue
-
Vol. 42,
no. 8
p. 112848
Abstract
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.
