The stability of the myelinating oligodendrocyte transcriptome is regulated by the nuclear lamina.
CP: Neuroscience
brain
chromatin
epigenetics
myelin
nucleus
progenitors
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
29 08 2023
29 08 2023
Historique:
received:
11
01
2023
revised:
26
05
2023
accepted:
07
07
2023
medline:
4
9
2023
pubmed:
29
7
2023
entrez:
29
7
2023
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 37515770
pii: S2211-1247(23)00859-8
doi: 10.1016/j.celrep.2023.112848
pmc: PMC10600948
mid: NIHMS1928236
pii:
doi:
Substances chimiques
Chromatin
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
112848Subventions
Organisme : NIMH NIH HHS
ID : U01 MH116442
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG050986
Pays : United States
Organisme : NINDS NIH HHS
ID : R35 NS111604
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH109677
Pays : United States
Organisme : NIH HHS
ID : OT2 OD030544
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG067025
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG065582
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH125246
Pays : United States
Organisme : NIDDK NIH HHS
ID : U2C DK119886
Pays : United States
Informations de copyright
Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests The authors declare no competing interests.
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