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| Status |
Public on Sep 12, 2022 |
| Title |
Mesenchymal stem cells derived from patients with premature ageing syndromes display hallmarks of physiological ageing [RNA-Seq] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Progeroid syndromes are rare genetic diseases with a majority of autosomal dominant transmission, the prevalence of which is less than 1 / 10,000,000. These syndromes caused by mutations in the LMNA gene encoding A-type Lamins belong to the group of disorders called laminopathies. Lamins are implicated in the architecture and function of the nucleus and chromatin. Patients affected with progeroid laminopathies display accelerated ageing of mesenchymal stem cells (MSCs)-derived tissues associated with nuclear morphological abnormalities. In order to identify pathways altered in progeroid patients’ MSCs, we used induced pluripotent stem cells (hiPSCs) from patients affected with classical Hutchinson-Gilford Progeria Syndrome (HGPS, c.1824C>T - p.G608G), HGPS-Like Syndrome (HGPS-L; c.1868C>G - p.T623S) associated with farnesylated prelamin A accumulation, or Atypical Progeroid Syndromes (APS; homozygous c.1583C> T - p.T528M; heterozygous c.1762T>C - p.C588R; compound heterozygous c.1583C>T and c.1619T>C - p.T528M and p.M540T) without progerin accumulation. By comparative analysis of the transcriptome and methylome of hiPSC-derived MSCs, we found that patient’s MSCs display specific DNA methylation patterns and modulated transcription at early stages of differentiation. We further explored selected biological processes deregulated in the presence of LMNA variants and confirmed alterations of age-related pathways during MSC differentiation. In particular, we report the presence of an altered mitochondrial pattern, an increased response to double-strand DNA damage and telomere erosion in HGPS, HGPS-L and APS MSCs, suggesting converging pathways, independent of progerin accumulation, but a distinct DNA methylation profile in HGPS and HGPS-L compared to APS cells.
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| Overall design |
Transcriptomic analysis of hIPSc and hIPSc derived MSC in HGPS, HGPS-l and APS
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| Contributor(s) |
Robin JD, Magdinier F, Trani J, Chevalier R |
| Citation(s) |
36104080 |
| |
| Submission date |
May 06, 2022 |
| Last update date |
Sep 27, 2022 |
| Contact name |
Frederique Magdinier |
| Organization name |
Aix-Marseille Université - Marseille Medical Genetics
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| Department |
MMG- U1251
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| Street address |
27 Bvd Jean Moulin, Aix-Marseille Université. Faculté de Médecine. Campus La Timone
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| City |
Marseille |
| ZIP/Postal code |
13005 |
| Country |
France |
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| Platforms (1) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
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| Samples (31)
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| This SubSeries is part of SuperSeries: |
| GSE202369 |
Mesenchymal stem cells derived from patients with premature ageing syndromes display hallmarks of physiological ageing |
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| Relations |
| BioProject |
PRJNA835734 |
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