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Ribonucleotide excision repair is essential to prevent skin cancer [CD49f+ epidermal cells]

ABSTRACT: Ribonucleotide excision repair is essential to prevent skin cancer [CD49f+ epidermal cells]

PROVIDER: PRJNA473507 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR7228800.fastq.gz	Fastqsanger.gz
	SRR7228810.fastq.gz	Fastqsanger.gz
	SRR7228801.fastq.gz	Fastqsanger.gz
	SRR7228811.fastq.gz	Fastqsanger.gz
	SRR7228792.fastq.gz	Fastqsanger.gz

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Ribonucleotide excision repair is essential to prevent skin cancer [CD45+ CD49f- epidermal cells]

Project description:Ribonucleotide excision repair is essential to prevent skin cancer [CD45+ CD49f- epidermal cells]

| PRJNA473510 | ENA

Ribonucleotide excision repair is essential to prevent skin cancer [CD49f+ epidermal cells]

Project description:Large numbers of ribonucleotides are incorporated into the eukaryotic nuclear genome during S-phase due to imperfect discrimination against ribonucleoside triphosphates by the replicative DNA polymerases. Ribonucleotides, by far the most common DNA lesion in replicating cells, destabilize the DNA, and an evolutionarily conserved DNA repair machinery, ribonucleotide excision repair (RER), ensures ribonucleotide removal. Complete lack of RER is embryonically lethal. Partial loss-of-function mutations in the genes encoding subunits of RNase H2, the enzyme essential for initiation of RER, cause the SLE-related type I interferonopathy Aicardi-Goutières syndrome. Here we establish that selective inactivation of RER in mouse epidermis results in spontaneous DNA damage, epidermal hyperproliferation associated with loss of hair follicle stem cells and hair follicle function. The animals develop keratinocyte intraepithelial neoplasia and invasive squamous cell carcinoma with complete penetrance, despite potent type I interferon production and skin inflammation. Compromised RER-mediated genome maintenance might represent an important tumor-promoting principle in human cancer.

2019-05-29 | GSE115003 | GEO

Ribonucleotide excision repair is essential to prevent skin cancer [CD45+ CD49f- epidermal cells]

2019-05-29 | GSE115004 | GEO

Ribonucleotide excision repair is essential to prevent skin cancer

Project description:Ribonucleotide excision repair is essential to prevent skin cancer

| PRJNA473504 | ENA

Ribonucleotide excision repair prevents intestinal tumorigenesis

Project description:Ribonucleotide excision repair prevents intestinal tumorigenesis

| PRJNA436583 | ENA

Ribonucleotide excision repair prevents intestinal tumorigenesis

Project description:Insufficient repair of DNA lesions results in the acquisition of somatic mutations and displays the driving force in cancerogenesis. Ribonucleotide incorporation by eukaryotic DNA polymerases occurs during every round of genome duplication and represents by far the most frequent type of naturally occurring DNA lesions. RNAse H2 removes misincorporated ribonucleotides from genomic DNA in a process termed ribonucleotide excision repair (RER). Whether intestinal epithelial proliferation requires RER and whether abrogation of RER is involved in the etiology of cancerogenesis at all is unknown. Mice with an epithelial specific deletion of RNase H2 subunit b (H2bΔIEC) and co-deletion of the tumor suppressor p53 (H2b/p53ΔIEC) were generated and phenotyped at young and old age. RNA sequencing was performed in isolated epithelial cells and intestinal organoids. Mutational signature of spontaneous tumors from H2b/p53ΔIEC mice were characterized using exome sequencing. Association of tumor RNase H2 expression and patient survival was assessed in transcriptome data from 467 CRC patients. H2bΔIEC mice display chronic epithelial DNA damage and develop a p53-dependent proliferative exhaustion of the intestinal stem cell compartment. H2b/p53ΔIEC mice have restored epithelial proliferation and spontaneously develop small intestinal carcinomas. Resulting tumors display a distinct mutational signature characterized by T>G base substitutions at GpTpG trinucleotides. Transcriptome data from human colorectal cancer patients indicate that reduced RNase H2 expression is associated with poor survival in CRC. Conclusion: We propose a hitherto unappreciated role for RNase H2 as a tumor suppressor gene in CRC. Our mouse model provides a novel tool to study the impact of abrogated RER on intestinal carcinogenesis.

2018-10-01 | GSE111318 | GEO

Ribonucleotide excision repair is essential to prevent skin cancer

Project description:This SuperSeries is composed of the SubSeries listed below.

2019-05-29 | GSE115005 | GEO

CD49f defines a subset of dysfunctional regulatory T cells circulating in the human peripheral blood

Project description:The therapeutic use of regulatory T cells (Tregs) in patients with autoimmune disorders has been hampered by the biological variability of memory Treg populations in the peripheral blood. In this study, we reveal through a combination of quantitative proteomic, multiparametric flow cytometry, RNA-seq data analysis and functional assays, that CD49f is heterogeneously expressed among human Tregs and impacts their immunomodulatory function. High expression of CD49f defines a subset of dysfunctional Tregs in the human blood characterized by a Th17-like phenotype and impaired suppressive capacity. CD49f is similarly distributed between naïve and memory Tregs and impacts the expression of CD39, CTLA-4, FoxP3 and CCR6 specifically in the memory compartment. Accumulation of CD49f high memory Tregs in the blood of ulcerative colitis patients correlates with disease severity. Our results highlight important considerations for Treg immunotherapy design in patients with inflammatory bowel disease which could possibly extend to other autoimmune disorders.

2021-08-06 | PXD022095 | Pride

The miRNA profiling of goat CD49f-positive and negative testicular cells

Project description:Purpose: miRNAs, a member of the small RNA, play critical roles in the mammalian spermatogenesis. Spermatogonia was the foundation of spermatogenesis and valuable for the study of spermatogenesis. However, it is still not clear that the expression profiling of the miRNAs in spermatogonia of dairy goat. Methods: The CD49f was one of the surface markers for spermatogonia enrichment by MACS. Therefore, we used CD49f microbeads antibody to purify CD49f-positive and negative cells of dairy goat testicular cells by MACS (Magnetic Activated Cell Sorting), and then in-depth analyzed the miRNA expression in these cells using Illumina sequencing technology. Results: The results of miRNAs expression profiling in purified CD49f-positive and negative testicular cells showed that 933 were miRNAs upregulated in CD49f-positive cells and 916 were miRNAs upregulated in CD49f-negative cells with a 2-fold increase, respectively; some spermatogonial stem cells(SSCs) specific miRNAs and marker genes in testis had a higher level expression in CD49f-positive testicular cells, such as miR-221, miR-23a, miR-29b, miR-24, miR-29a, miR-199b, miR-199a, miR-27a, miR-21. Conclusions: our comparative miRNAome data provided some useful miRNAs profiling data of dairy goat spermatogonia cells and suggested CD49f could be used to enrich dairy goat spermatogonia-like cells, including SSCs.

2014-04-25 | GSE57041 | GEO

RNA sequence of CD49f-positive mesenchymal populations in dermis of neonatal mice

Project description:We defined CD49f-high, CD49f-low and CD49f-neg mesenchymal subpopulations in the dermis. Transcriptome analysis revealed that CD49fhigh cells highly express gene regulatory network of neural crest cells, while CD49flow cells were enriched with melanocyte lineage development and maintenance related genes. The identity and function of above cell populations were further verified by lineage tracing.

2019-08-16 | GSE135471 | GEO

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