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| Status |
Public on Feb 04, 2020 |
| Title |
Polycomb dysfunctional transcriptional repression in muscle stem cells contributes to lamin dependent muscular dystrophy [RNA-seq] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Polycomb group of proteins (PcG) and the nuclear Lamin A are key factors in the maintenance of chromatin higher order structures required for preserving cell identity. Mutations in the Lamin A/C gene cause several diseases, belonging to the class of laminopathies, including Emery-Dreifuss Muscular Dystrophy. Nevertheless, epigenetic mechanisms involved in the pathogenesis of lamin-dependent dystrophy are still largely unknown. We show that Lamin A loss causes deregulated PcG positioning in muscular stem cells followed by upregulation of adipogenic markers and induction of the senescence’s driver p16INK4a from Cdkn2a locus. This aberrant transcriptional programme causes impairment in self-renewal, loss of cell identity and premature exhaustion of quiescent satellite cell pool. Genetic ablation of Cdkn2a locus restores muscle growth and muscle stem cell properties in Lamin A/C null dystrophic mice. In conclusion, our findings suggest that Lamin A has an essential role in preserving satellite cell self-renewal capacity and indicate that Lamin A-dependent muscular dystrophy can be ascribed to intrinsic epigenetic dysfunctions of muscle stem cells
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| |
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| Overall design |
Transcriptional and epigenetic profiling of Lmna Δ8-11 +/+ and Lmna Δ8-11 -/- mice
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| |
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| Contributor(s) |
Lanzuolo C, Bianchi A, Lucini F |
| Citation(s) |
31999646 |
| |
| Submission date |
Dec 12, 2018 |
| Last update date |
May 05, 2020 |
| Contact name |
Chiara Lanzuolo |
| E-mail(s) |
lanzuolo@ingm.org
|
| Phone |
0200660358
|
| Organization name |
CNR and Istituto Nazionale Genetica Molecolare
|
| Lab |
Lanzuolo Lab
|
| Street address |
Via Francesco Sforza 35
|
| City |
Milan |
| State/province |
--- |
| ZIP/Postal code |
20122 |
| Country |
Italy |
| |
|
| Platforms (1) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
|
| Samples (6)
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| This SubSeries is part of SuperSeries: |
| GSE123725 |
Polycomb dysfunctional transcriptional repression in muscle stem cells contributes to lamin dependent muscular dystrophy |
|
| Relations |
| BioProject |
PRJNA509645 |
| SRA |
SRP173336 |
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