Differential roles of epigenetic regulators in the survival and differentiation of oligodendrocyte precursor cells.
Animals
Animals, Newborn
Cell Differentiation
Cerebral Cortex
/ cytology
DNA (Cytosine-5-)-Methyltransferases
/ genetics
DNA Methylation
/ drug effects
DNA Methyltransferase 3A
Epigenesis, Genetic
/ physiology
Green Fluorescent Proteins
/ genetics
Histone Deacetylases
/ genetics
Myelin Basic Protein
/ genetics
Oligodendrocyte Precursor Cells
/ physiology
RNA, Messenger
/ metabolism
RNA, Small Interfering
/ genetics
Rats
Rats, Sprague-Dawley
Receptor, Platelet-Derived Growth Factor alpha
/ genetics
Transfection
DNMT
HDAC
cell differentiation
epigenetic regulator
oligodendrocyte precursor cell
Journal
Glia
ISSN: 1098-1136
Titre abrégé: Glia
Pays: United States
ID NLM: 8806785
Informations de publication
Date de publication:
04 2019
04 2019
Historique:
received:
20
11
2017
revised:
23
10
2018
accepted:
23
10
2018
entrez:
23
2
2019
pubmed:
23
2
2019
medline:
14
6
2019
Statut:
ppublish
Résumé
During development or after brain injury, oligodendrocyte precursor cells (OPCs) differentiate into oligodendrocytes to supplement the number of oligodendrocytes. Although mechanisms of OPC differentiation have been extensively examined, the role of epigenetic regulators, such as histone deacetylases (HDACs) and DNA methyltransferase enzymes (DNMTs), in this process is still mostly unknown. Here, we report the differential roles of epigenetic regulators in OPC differentiation. We prepared primary OPC cultures from neonatal rat cortex. Our cultured OPCs expressed substantial amounts of mRNA for HDAC1, HDAC2, DNMT1, and DNMT3a. mRNA levels of HDAC1 and HDAC2 were both decreased by the time OPCs differentiated into myelin-basic-protein expressing oligodendrocytes. However, DNMT1 or DNMT3a mRNA level gradually decreased or increased during the differentiation step, respectively. We then knocked down those regulators in cultured OPCs with siRNA technique before starting OPC differentiation. While HDAC1 knockdown suppressed OPC differentiation, HDAC2 knockdown promoted OPC differentiation. DNMT1 knockdown also suppressed OPC differentiation, but unlike HDAC1/2, DNMT1-deficient cells showed cell damage during the later phase of OPC differentiation. On the other hand, when OPCs were transfected with siRNA for DNMT3a, the number of OPCs was decreased, indicating that DNMT3a may participate in OPC survival/proliferation. Taken together, these data demonstrate that each epigenetic regulator has different phase-specific roles in OPC survival and differentiation.
Identifiants
pubmed: 30793389
doi: 10.1002/glia.23567
pmc: PMC6573028
mid: NIHMS1027190
doi:
Substances chimiques
Myelin Basic Protein
0
RNA, Messenger
0
RNA, Small Interfering
0
Green Fluorescent Proteins
147336-22-9
DNA (Cytosine-5-)-Methyltransferases
EC 2.1.1.37
DNA Methyltransferase 3A
EC 2.1.1.37
Receptor, Platelet-Derived Growth Factor alpha
EC 2.7.10.1
Histone Deacetylases
EC 3.5.1.98
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
718-728Subventions
Organisme : NINDS NIH HHS
ID : P01 NS055104R01 NS065089
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS093415
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS067139
Pays : United States
Organisme : NINDS NIH HHS
ID : R21 NS113065
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS065089
Pays : United States
Organisme : NIH HHS
Pays : United States
Organisme : NINDS NIH HHS
ID : P01 NS055104
Pays : United States
Informations de copyright
© 2018 Wiley Periodicals, Inc.
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