Insights into Epithelial Cell Senescence from Transcriptome and Secretome Analysis of Human Oral Keratinocytes [DNA-Seq]
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA691946 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR13429768_1.fastq.gz | Fastqsanger.gz | |||
| SRR13429768_2.fastq.gz | Fastqsanger.gz | |||
| SRR13429769_1.fastq.gz | Fastqsanger.gz | |||
| SRR13429769_2.fastq.gz | Fastqsanger.gz |
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Project description:Insights into Epithelial Cell Senescence from Transcriptome and Secretome Analysis of Human Oral Keratinocytes
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Project description:Insights into Epithelial Cell Senescence from Transcriptome and Secretome Analysis of Human Oral Keratinocytes [RNA-seq]
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Project description:Senescent cells are one source of the chronic inflammation that contributes to the diseases and debilities of aging. Whereas cellular senescence in fibroblasts is well documented, how this process is orchestrated in epithelial cells, the origin of human carcinomas, is much less understood. We used normal primary human oral keratinocytes (NOKs) to elucidate senescence programs in a prototype mucosal epithelial cell that undergoes senescence spontaneously. We employed widely-accepted assays to characterize senescence phenotypes in these cells and found that p21WAF1/CIP1 is not a reliable marker of senescence for NOKs, as it is for fibroblasts. We performed transcriptome analysis by RNA-seq and proteomic analysis of secreted proteins, both non-vesicular and those associated with extracellular vesicles (EVs). NOKs, while sharing with fibroblasts certain important aspects of inflammation, such as upregulation of the NF-κB, interferon, and p38MAPK pathways, also exhibit novel senescence associated characteristics. In two of the donors, we observed an expected repression of DNA repair genes, correlating with downregulation of E2F1 mRNA and protein, but saw a divergent result for the third donor. We were able to highlight potential senolytic targets. Our secretome analysis led us to propose additions to the senescence associated secretory phenotype, including HSP60, which we found on the surface of EVs. Moreover, EVs from senescent NOKs can create inflammation by stimulating interferon pathway signaling in THP-1 monocytes in culture. Our results highlight important senescence changes in epithelial cells in terms of how these cells contribute to chronic inflammation, aging, and age-related diseases.
2021-03-18 | GSE155371 | GEO
Project description:Senescent cells are one source of the chronic inflammation that contributes to the diseases and debilities of aging. Whereas cellular senescence in fibroblasts is well documented, how this process is orchestrated in epithelial cells, the origin of human carcinomas, is much less understood. We used normal primary human oral keratinocytes (NOKs) to elucidate senescence programs in a prototype mucosal epithelial cell that undergoes senescence spontaneously. We employed widely-accepted assays to characterize senescence phenotypes in these cells and found that p21WAF1/CIP1 is not a reliable marker of senescence for NOKs, as it is for fibroblasts. We performed transcriptome analysis by RNA-seq and proteomic analysis of secreted proteins, both non-vesicular and those associated with extracellular vesicles (EVs). NOKs, while sharing with fibroblasts certain important aspects of inflammation, such as upregulation of the NF-κB, interferon, and p38MAPK pathways, also exhibit novel senescence associated characteristics. In two of the donors, we observed an expected repression of DNA repair genes, correlating with downregulation of E2F1 mRNA and protein, but saw a divergent result for the third donor. We were able to highlight potential senolytic targets. Our secretome analysis led us to propose additions to the senescence associated secretory phenotype, including HSP60, which we found on the surface of EVs. Moreover, EVs from senescent NOKs can create inflammation by stimulating interferon pathway signaling in THP-1 monocytes in culture. Our results highlight important senescence changes in epithelial cells in terms of how these cells contribute to chronic inflammation, aging, and age-related diseases.
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Project description:Senescent cells produce chronic inflammation that contributes to the diseases and debilities of aging. How this process is orchestrated in epithelial cells, the origin of human carcinomas, is poorly understood. We used human normal oral keratinocytes (NOKs) to elucidate senescence programs in a prototype primary mucosal epithelial cell that senesces spontaneously. While NOKs exhibit several typical facets of senescence, they also display distinct characteristics. These include expression of p21WAF1/CIP1 at early passages, making this common marker of senescence unreliable in NOKs. Transcriptome analysis by RNA-seq revealed specific commonalities with and differences from cancer cells, explicating the tumor avoidance role of senescence. Repression of DNA repair genes that correlated with downregulation of E2F1 mRNA and protein was observed for two donors; a divergent result was seen for the third. Using proteomic profiling of soluble (non-vesicular) and extracellular vesicle (EV) associated secretions, we propose additions to the senescence associated secretory phenotype, including HSP60, which localizes to the surface of EVs. Finally, EVs from senescent NOKs activate interferon pathway signaling in THP-1 monocytes in a STING-dependent manner and associate with mitochondrial and nuclear DNA. Our results highlight senescence changes in epithelial cells and how they might contribute to chronic inflammation and age-related diseases.
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Project description:The morphology and the behavior of skin and oral tissue keratinocytes are different. One significant dissimilarity between the two sites is the response to injury. Oral and skin keratinocytes have intrinsic differences in the response to injury and such differences are reflected in gene expression profiles. We used microarrays to investigate differences in global gene expression patterns between baseline skin and oral epithelium sheets without their underlying connective tissue.
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Project description:This was a hypothesis generating experiment to look at miR expression in a range of oral keratinocytes, including normal, precancer and oral cancer samples. The cells were cultures as per standard protocols (duplicate cultures) before assessment on the Affy miRNA array (1.0)
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