Similar Datasets
Project description:Xeroderma pigmentosum (XP) is caused by defective nucleotide excision-repair of DNA damage. This results in hypersensitivity to ultraviolet light and increased skin cancer risk, as sunlight-induced photoproducts remain unrepaired. However, many XP patients also display early-onset neurodegeneration, which leads to premature death. The mechanism of neurodegeneration is unknown. Here, we investigate XP neurodegeneration using pluripotent stem cells derived from XP patients and healthy relatives, performing functional multi-omics on samples during neuronal differentiation. We show substantially increased levels of 5',8-cyclopurine and 8-oxopurine in XP neuronal DNA secondary to marked oxidative stress. Furthermore, we find that the endoplasmic reticulum stress response is upregulated and reversal of the mutant genotype is associated with phenotypic rescue. Critically, XP neurons exhibit inappropriate downregulation of the protein clearance ubiquitin-proteasome system (UPS). Chemical enhancement of UPS activity in XP neuronal models improves phenotypes, albeit inadequately. Although more work is required, this study presents insights with intervention potential.
2024-04-18 | PXD047571 | Pride
Project description:Xeroderma Pigmentosum (XP) is a DNA repair disorder characterized by photosensitivity, resulting in occurrence of freckle-like pigmented maculae and depigmented maculae on sun-exposed areas. XP complementation group A (XP-A) is the most frequent type in Japan, and patients with XP-A present most severe cutaneous and neurological symptoms due to nucleotide excision repair deficiency. Here, we established induced pluripotent stem cells (iPSCs) derived from XP-A patients and successfully differentiated into melanocytes. To elucidate the pathophysiology of XP, we comprehensively analyzed the difference in gene expression between XP-A-iMCs and healthy-control-iPSC-derived melanocytes (HC-iMCs) 4 hours and 12 hours after irradiation with 30 J/m2 or 150 J/m2 of UV-B using microarray analysis.
2022-01-01 | GSE185308 | GEO
Project description:XPA is required for Nucleotide Excision Repair system, which could function to repair DNA damage induced by the UV. UV damage on the genomic DNA cannot be removed, thus persistence of damage could affect the transcriptional machinary. We used the microarray to investigate the global expression profiles in the XP-A and XP-V cells in the low dose of UVC comparing with fibroblast from healthy person. Human primary fibroblasts were developed from the skin of healthy person and two XP patients (XP-A and XP-V). We evaluated global expression profiles comparing the UVC-exposed (0.5J/m2, 5J/m2) with non-exposed sample.
2015-07-14 | E-GEOD-70818 | biostudies-arrayexpress
Project description:Xeroderma Pigmentosum (XP) is a rare autosomal genetic disease. XP patients present a default in the mechanism responsible for the repair of UV-induced DNA lesions. They are prone to develop skin cancers with high frequencies early in their life. To identify microenvironment factors that could contribute to the progression of skin cancers in XP-C group we did comparative transcriptomic analysis of WT and XP-C dermal patient’s fibroblasts.
2019-09-19 | GSE133084 | GEO
Project description:This is a first-in-human multi-center study which will be conducted in advanced malignant solid tumors patients. The solid tumor type is limited to melanoma, colorectal, non-small-cell lung, and thyroid cancer with positive BRAF V600 mutation. This study is divided into three stages: Phase Ia: a dose-escalation phase of XP-102; Phase Ib: a dose-escalation and sample size expansion phase of XP-102 plus trametinib; Phase IIa: an expansion phase of XP-102 plus trametinib.
| 2708993 | ecrin-mdr-crc
Project description:To compare gene expression between the materal X (Xm) and paternal X (Xp), we used a flurorescence-based cell sorting to separate the maternal X from the paternal X. Then we performed gene expression analysis using data obtained from RNA-seq of young Xm and Xp cells To compare gene expression between the materal X (Xm) and paternal X (Xp) in neurons from both young and old mice, we used a flurorescence-based cell sorting to separate the maternal X from the paternal X. Then we performed gene expression analysis using data obtained from RNA-seq of young and old Xm and Xp neurons.
2024-11-06 | GSE200461 | GEO
Project description:Expression data from XP-A and XP-V cells after UVC exposure
| PRJNA289648 | ENA
Project description:Rhodococcus erythropolis XP Genome Sequencing
| PRJNA72225 | ENA
Project description:XP-8 Raw sequence reads
| PRJNA376863 | ENA