Single-Cell Transcriptomics Reveals the Expression of Aging- and Senescence-Associated Genes in Distinct Cancer Cell Populations

The human aging process is associated with molecular changes and cellular degeneration, resulting in a significant increase in cancer incidence with age. Despite their potential correlation, the relationship between cancer- and ageing-related transcriptional changes is largely unknown. In this study...

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Main Authors: Dominik Saul, Robyn Laura Kosinsky
Format: Article
Language:English
Published: MDPI AG 2021-11-01
Series:Cells
Subjects:
Online Access:https://www.mdpi.com/2073-4409/10/11/3126
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author Dominik Saul
Robyn Laura Kosinsky
author_facet Dominik Saul
Robyn Laura Kosinsky
author_sort Dominik Saul
collection DOAJ
description The human aging process is associated with molecular changes and cellular degeneration, resulting in a significant increase in cancer incidence with age. Despite their potential correlation, the relationship between cancer- and ageing-related transcriptional changes is largely unknown. In this study, we aimed to analyze aging-associated transcriptional patterns in publicly available bulk mRNA-seq and single-cell RNA-seq (scRNA-seq) datasets for chronic myelogenous leukemia (CML), colorectal cancer (CRC), hepatocellular carcinoma (HCC), lung cancer (LC), and pancreatic ductal adenocarcinoma (PDAC). Indeed, we detected that various aging/senescence-induced genes (ASIGs) were upregulated in malignant diseases compared to healthy control samples. To elucidate the importance of ASIGs during cell development, pseudotime analyses were performed, which revealed a late enrichment of distinct cancer-specific ASIG signatures. Notably, we were able to demonstrate that all cancer entities analyzed in this study comprised cell populations expressing ASIGs. While only minor correlations were detected between ASIGs and transcriptome-wide changes in PDAC, a high proportion of ASIGs was induced in CML, CRC, HCC, and LC samples. These unique cellular subpopulations could serve as a basis for future studies on the role of aging and senescence in human malignancies.
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spelling doaj.art-5706033af5564384b011ff7e4d34807b2023-11-22T22:51:41ZengMDPI AGCells2073-44092021-11-011011312610.3390/cells10113126Single-Cell Transcriptomics Reveals the Expression of Aging- and Senescence-Associated Genes in Distinct Cancer Cell PopulationsDominik Saul0Robyn Laura Kosinsky1Division of Endocrinology, Mayo Clinic, Rochester, MN 55902, USADivision of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55902, USAThe human aging process is associated with molecular changes and cellular degeneration, resulting in a significant increase in cancer incidence with age. Despite their potential correlation, the relationship between cancer- and ageing-related transcriptional changes is largely unknown. In this study, we aimed to analyze aging-associated transcriptional patterns in publicly available bulk mRNA-seq and single-cell RNA-seq (scRNA-seq) datasets for chronic myelogenous leukemia (CML), colorectal cancer (CRC), hepatocellular carcinoma (HCC), lung cancer (LC), and pancreatic ductal adenocarcinoma (PDAC). Indeed, we detected that various aging/senescence-induced genes (ASIGs) were upregulated in malignant diseases compared to healthy control samples. To elucidate the importance of ASIGs during cell development, pseudotime analyses were performed, which revealed a late enrichment of distinct cancer-specific ASIG signatures. Notably, we were able to demonstrate that all cancer entities analyzed in this study comprised cell populations expressing ASIGs. While only minor correlations were detected between ASIGs and transcriptome-wide changes in PDAC, a high proportion of ASIGs was induced in CML, CRC, HCC, and LC samples. These unique cellular subpopulations could serve as a basis for future studies on the role of aging and senescence in human malignancies.https://www.mdpi.com/2073-4409/10/11/3126canceragingsingle-cell sequencinggene expressiontranscriptomicsnext-generation sequencing
spellingShingle Dominik Saul
Robyn Laura Kosinsky
Single-Cell Transcriptomics Reveals the Expression of Aging- and Senescence-Associated Genes in Distinct Cancer Cell Populations
Cells
cancer
aging
single-cell sequencing
gene expression
transcriptomics
next-generation sequencing
title Single-Cell Transcriptomics Reveals the Expression of Aging- and Senescence-Associated Genes in Distinct Cancer Cell Populations
title_full Single-Cell Transcriptomics Reveals the Expression of Aging- and Senescence-Associated Genes in Distinct Cancer Cell Populations
title_fullStr Single-Cell Transcriptomics Reveals the Expression of Aging- and Senescence-Associated Genes in Distinct Cancer Cell Populations
title_full_unstemmed Single-Cell Transcriptomics Reveals the Expression of Aging- and Senescence-Associated Genes in Distinct Cancer Cell Populations
title_short Single-Cell Transcriptomics Reveals the Expression of Aging- and Senescence-Associated Genes in Distinct Cancer Cell Populations
title_sort single cell transcriptomics reveals the expression of aging and senescence associated genes in distinct cancer cell populations
topic cancer
aging
single-cell sequencing
gene expression
transcriptomics
next-generation sequencing
url https://www.mdpi.com/2073-4409/10/11/3126
work_keys_str_mv AT dominiksaul singlecelltranscriptomicsrevealstheexpressionofagingandsenescenceassociatedgenesindistinctcancercellpopulations
AT robynlaurakosinsky singlecelltranscriptomicsrevealstheexpressionofagingandsenescenceassociatedgenesindistinctcancercellpopulations