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| Status |
Public on Aug 16, 2021 |
| Title |
PARP1-mediated PARylation activity is essential for oligodendroglial differentiation and CNS myelination |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
The function of poly(ADP-ribosyl) polymerase 1 (PARP1) in myelination and remyelination of the central nervous system (CNS) remains enigmatic. Here we report that PARP1 is an intrinsic driver for oligodendroglial development and myelination. Genetic PARP1 depletion impairs the differentiation of oligodendrocyte progenitor cells (OPCs) into oligodendrocytes and impedes CNS myelination. Mechanistically, PARP1-mediated PARylation activity is not only necessary but also sufficient for OPC differentiation. At the molecular level, we identify the RNA-binding protein Myef2 as a PARylated target which controls OPC differentiation through PARylation-modulated de-repression of myelin protein expression. Furthermore, PARP1’s enzymatic activity is necessary for oligodendrocyte and myelin regeneration after demyelination. Together, our findings suggest that PARP1-mediated PARylation activity may be a potential therapeutic target for promoting OPC differentiation and remyelination in neurological disorders characterized by arrested OPC differentiation and remyelination failure such as multiple sclerosis.
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| Overall design |
Three Parp1 cKO mice and three littermate control mice (both sexes) were injected with tamoxifen at P1, P2, and P3 and the brain was harvested for total RNA extraction and NGS RNS-sequencing. Downstream analysis was followed to assess the gene expression level across the 6 samples.
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| Contributor(s) |
Guo F, Wang Y |
| Citation(s) |
34610310 |
| |
| Submission date |
Aug 11, 2021 |
| Last update date |
Nov 15, 2021 |
| Contact name |
Fuzheng Guo |
| E-mail(s) |
[email protected]
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| Phone |
9164535026
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| Organization name |
University of California Davis
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| Street address |
2425 Stockton Blvd
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| City |
Sacramento |
| State/province |
CA |
| ZIP/Postal code |
95817 |
| Country |
USA |
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| Platforms (1) |
| GPL21103 |
Illumina HiSeq 4000 (Mus musculus) |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA753878 |
| SRA |
SRP332134 |
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