DNA methylation of fibroblasts from one HGPS patient
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PROVIDER: PRJNA803475 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:DNAm profiling of fibroblasts from one HGPS patient (6 years; 3 replicates assessed) and two healthy controls (12 and 15 years, each assessed in 2 replicates)
2023-10-26 | GSE196148 | GEO
Project description:We analyzed and compared global gene expression changes in fibroblasts from human subjects with HGPS compared to age matched controls. We then treated both control and HGPS fibroblasts with a protein farnesyltransferase inhibitor (FTI), a medication currently used in clinical trials to treat HGPS, to look for a reversal of the gene defects present in HGPS fibroblasts.
2010-06-01 | E-MEXP-2597 | biostudies-arrayexpress
Project description:Primary skin fibroblasts from a HGPS patient and an age-matched control wild-type individual were challenged in a standard transformation assay by retroviral introduction of TERT (T), V12-HRAS (R) and SV40 large and small T antigens (S). Knock-down of BRD4 in this TRS-HGPS cell line (TRS-HGPS-shBRD4) was achieved by retroviral introduction of independent shRNAs (shBRD4-1 to -3) Abstract: Advanced age and DNA damage accumulation are strong risk factors for cancer. The premature-aging disorder Hutchinson Gilford Progeria Syndrome (HGPS) provides a unique opportunity to study the interplay between DNA damage and aging-associated tumor mechanisms, since HGPS patients do not develop tumors despite elevated levels of DNA damage. Here, we have used HGPS patient cells to identify a protective mechanism to oncogenesis. We find that HGPS cells are resistant to neo-plastic transformation. This resistance is mediated by the bromodomain protein BRD4, which exhibits altered genome-wide binding patterns in transformation-resistant cells leading to inhibition of oncogenic de-differentiation. BRD4 also in-hibits, albeit to a lower extent, the tumorigenic potential of transformed cells from healthy individuals and BRD4-mediated tumor protection is clinically relevant, since a BRD4 gene signature predicts positive clinical outcome in breast and lung cancer. Our results demonstrate a protective function for BRD4 and suggest tissue-specific functions for BRD4 in tumorigenesis. 2 biological replicates are included for TRS-WT and TRS-HGPS cell lines. 3 biological replicates are included for TRS-HGPS-shBRD4 (derived from 3 independent shRNAs against BRD4)
2014-10-02 | E-GEOD-60519 | biostudies-arrayexpress
Project description:Premature aging disorders provide a lens through which to study the drivers of aging. In Hutchinson-Gilford progeria syndrome (HGPS) a mutant form of the nuclear scaffold protein lamin A distorts nuclei and sequesters nuclear proteins. We used stable isotope labeling and quantitative mass spectrometry to investigate nuclear protein homeostasis in primary HGPS-derived cells.
2017-07-07 | PXD006016 | Pride
Project description:Primary skin fibroblasts from a HGPS patient and an age-matched control wild-type individual were challenged in a standard transformation assay by retroviral introduction of TERT (T), V12-HRAS (R) and SV40 large and small T antigens (S). Knock-down of BRD4 in this TRS-HGPS cell line (TRS-HGPS-shBRD4) was achieved by retroviral introduction of independent shRNAs (shBRD4-1 to -3) Abstract: Advanced age and DNA damage accumulation are strong risk factors for cancer. The premature-aging disorder Hutchinson Gilford Progeria Syndrome (HGPS) provides a unique opportunity to study the interplay between DNA damage and aging-associated tumor mechanisms, since HGPS patients do not develop tumors despite elevated levels of DNA damage. Here, we have used HGPS patient cells to identify a protective mechanism to oncogenesis. We find that HGPS cells are resistant to neo-plastic transformation. This resistance is mediated by the bromodomain protein BRD4, which exhibits altered genome-wide binding patterns in transformation-resistant cells leading to inhibition of oncogenic de-differentiation. BRD4 also in-hibits, albeit to a lower extent, the tumorigenic potential of transformed cells from healthy individuals and BRD4-mediated tumor protection is clinically relevant, since a BRD4 gene signature predicts positive clinical outcome in breast and lung cancer. Our results demonstrate a protective function for BRD4 and suggest tissue-specific functions for BRD4 in tumorigenesis.
2014-10-02 | GSE60519 | GEO
Project description:Hutchinson-Gilford Progeria Syndrome (HGPS) is a segmental premature aging disorder caused by the accumulation of the truncated form of Lamin A known as Progerin within the nuclear lamina. Cellular hallmarks of HGPS include nuclear blebbing, loss of peripheral heterochromatin, defective epigenetic inheritance, altered gene expression, and senescence. To model HGPS using iPSCs, detailed genome-wide and structural analysis of the epigenetic landscape is required to assess the initiation and progression of the disease. We generated a library of iPSC lines from fibroblasts of HGPS patients and controls, including one family trio. Our microarray results suggest that despite the presence of defects associated with Progerin in the nuclear lamina including structural defects, senescence and abnormal epigenetic marks, HGPS fibroblasts can be reprogrammed into iPSCs with transcriptomes that are essentially identical to control iPSCs and hESCs.
2020-01-02 | GSE84351 | GEO
Project description:Primary skin fibroblasts from HGPS patients and an age-matched control wild-type individuals were challenged in a standard transformation assay by retroviral introduction of TERT (T), V12-HRAS (R) and SV40 large and small T antigens (S). TERT-Immortalized cell lines from the same sources were also generated. Abstract: Advanced age and DNA damage accumulation are strong risk factors for cancer. The premature-aging disorder Hutchinson Gilford Progeria Syndrome (HGPS) provides a unique opportunity to study the interplay between DNA damage and aging-associated tumor mechanisms, since HGPS patients do not develop tumors despite elevated levels of DNA damage. Here, we have used HGPS patient cells to identify a protective mechanism to oncogenesis. We find that HGPS cells are resistant to neo-plastic transformation. This resistance is mediated by the bromodomain protein BRD4, which exhibits altered genome-wide binding patterns in transformation-resistant cells leading to inhibition of oncogenic de-differentiation. BRD4 also in-hibits, albeit to a lower extent, the tumorigenic potential of transformed cells from healthy individuals and BRD4-mediated tumor protection is clinically relevant, since a BRD4 gene signature predicts positive clinical outcome in breast and lung cancer. Our results demonstrate a protective function for BRD4 and suggest tissue-specific functions for BRD4 in tumorigenesis. 2 independent cell lines are included for each of the 4 groups (TERT-WT, TRS-WT, TERT-HGPS and TRS-HGPS)
2014-10-02 | E-GEOD-60518 | biostudies-arrayexpress
Project description:Premature aging disorders provide a lens through which to study the drivers of aging. In Hutchinson-Gilford progeria syndrome (HGPS) a mutant form of the nuclear scaffold protein lamin A distorts nuclei and sequesters nuclear proteins. We used stable isotope labeling and quantitative mass spectrometry to investigate nuclear protein homeostasis in primary HGPS-derived cells.
2017-07-07 | PXD006015 | Pride
Project description:Primary skin fibroblasts from HGPS patients and an age-matched control wild-type individuals were challenged in a standard transformation assay by retroviral introduction of TERT (T), V12-HRAS (R) and SV40 large and small T antigens (S). TERT-Immortalized cell lines from the same sources were also generated. Abstract: Advanced age and DNA damage accumulation are strong risk factors for cancer. The premature-aging disorder Hutchinson Gilford Progeria Syndrome (HGPS) provides a unique opportunity to study the interplay between DNA damage and aging-associated tumor mechanisms, since HGPS patients do not develop tumors despite elevated levels of DNA damage. Here, we have used HGPS patient cells to identify a protective mechanism to oncogenesis. We find that HGPS cells are resistant to neo-plastic transformation. This resistance is mediated by the bromodomain protein BRD4, which exhibits altered genome-wide binding patterns in transformation-resistant cells leading to inhibition of oncogenic de-differentiation. BRD4 also in-hibits, albeit to a lower extent, the tumorigenic potential of transformed cells from healthy individuals and BRD4-mediated tumor protection is clinically relevant, since a BRD4 gene signature predicts positive clinical outcome in breast and lung cancer. Our results demonstrate a protective function for BRD4 and suggest tissue-specific functions for BRD4 in tumorigenesis.
2014-10-02 | GSE60518 | GEO
Project description:Gene expression profiling of AOS Patient fibroblasts against Control fibroblasts
2025-01-23 | E-MTAB-5067 | ExpressionAtlas