Analysis at the single-cell level indicates an important role of heterogeneous global DNA methylation status on the progression of lung adenocarcinoma

Abstract Aberrant DNA modifications affect the tumorigenesis and progression of lung cancer. However, the global methylation status of tumor cells and the heterogeneous methylation status of cells within the same tumor need further study. We used publicly available single-cell RNAseq data to investi...

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Autores principales: Quan-Fang Chen, Han Gao, Qing-Yun Pan, Ying-Ju Wang, Xiao-Ning Zhong
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Publicado: Nature Portfolio 2021
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Acceso en línea:https://doaj.org/article/56ccb5b3517e4e4187a760697307ad60
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spelling oai:doaj.org-article:56ccb5b3517e4e4187a760697307ad602021-12-05T12:14:49ZAnalysis at the single-cell level indicates an important role of heterogeneous global DNA methylation status on the progression of lung adenocarcinoma10.1038/s41598-021-02786-y2045-2322https://doaj.org/article/56ccb5b3517e4e4187a760697307ad602021-12-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-02786-yhttps://doaj.org/toc/2045-2322Abstract Aberrant DNA modifications affect the tumorigenesis and progression of lung cancer. However, the global methylation status of tumor cells and the heterogeneous methylation status of cells within the same tumor need further study. We used publicly available single-cell RNAseq data to investigate the impact and diversity of global methylation status on lung adenocarcinoma. Clustering cells into subgroups and cell differentiation pseudotime analysis, based on expression profile, demonstrated that the global methylation status was crucial to lung adenocarcinoma function and progression. Hypermethylated tumor cells had increased activity related to the hypoxia response. Hyper- and hypomethylated cells indicated upregulation in pathways involving focal adhesion and cell junctions. Pseudotime analysis showed that cell clusters with unique methylation activities were located at the ends of the putative trajectories, suggesting that DNA methylation and demethylation activities were essential to tumor cell progression. Expression of SPP1 was associated with the global methylation status of tumor cells and with patient prognosis. Our study identified the importance and diversity of global DNA methylation status by analysis at the single-cell level. Our findings provide new information about the global DNA methylation status of tumor cells and suggest new approaches for precision medical treatments for lung adenocarcinoma.Quan-Fang ChenHan GaoQing-Yun PanYing-Ju WangXiao-Ning ZhongNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Quan-Fang Chen
Han Gao
Qing-Yun Pan
Ying-Ju Wang
Xiao-Ning Zhong
Analysis at the single-cell level indicates an important role of heterogeneous global DNA methylation status on the progression of lung adenocarcinoma
description Abstract Aberrant DNA modifications affect the tumorigenesis and progression of lung cancer. However, the global methylation status of tumor cells and the heterogeneous methylation status of cells within the same tumor need further study. We used publicly available single-cell RNAseq data to investigate the impact and diversity of global methylation status on lung adenocarcinoma. Clustering cells into subgroups and cell differentiation pseudotime analysis, based on expression profile, demonstrated that the global methylation status was crucial to lung adenocarcinoma function and progression. Hypermethylated tumor cells had increased activity related to the hypoxia response. Hyper- and hypomethylated cells indicated upregulation in pathways involving focal adhesion and cell junctions. Pseudotime analysis showed that cell clusters with unique methylation activities were located at the ends of the putative trajectories, suggesting that DNA methylation and demethylation activities were essential to tumor cell progression. Expression of SPP1 was associated with the global methylation status of tumor cells and with patient prognosis. Our study identified the importance and diversity of global DNA methylation status by analysis at the single-cell level. Our findings provide new information about the global DNA methylation status of tumor cells and suggest new approaches for precision medical treatments for lung adenocarcinoma.
format article
author Quan-Fang Chen
Han Gao
Qing-Yun Pan
Ying-Ju Wang
Xiao-Ning Zhong
author_facet Quan-Fang Chen
Han Gao
Qing-Yun Pan
Ying-Ju Wang
Xiao-Ning Zhong
author_sort Quan-Fang Chen
title Analysis at the single-cell level indicates an important role of heterogeneous global DNA methylation status on the progression of lung adenocarcinoma
title_short Analysis at the single-cell level indicates an important role of heterogeneous global DNA methylation status on the progression of lung adenocarcinoma
title_full Analysis at the single-cell level indicates an important role of heterogeneous global DNA methylation status on the progression of lung adenocarcinoma
title_fullStr Analysis at the single-cell level indicates an important role of heterogeneous global DNA methylation status on the progression of lung adenocarcinoma
title_full_unstemmed Analysis at the single-cell level indicates an important role of heterogeneous global DNA methylation status on the progression of lung adenocarcinoma
title_sort analysis at the single-cell level indicates an important role of heterogeneous global dna methylation status on the progression of lung adenocarcinoma
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/56ccb5b3517e4e4187a760697307ad60
work_keys_str_mv AT quanfangchen analysisatthesinglecelllevelindicatesanimportantroleofheterogeneousglobaldnamethylationstatusontheprogressionoflungadenocarcinoma
AT hangao analysisatthesinglecelllevelindicatesanimportantroleofheterogeneousglobaldnamethylationstatusontheprogressionoflungadenocarcinoma
AT qingyunpan analysisatthesinglecelllevelindicatesanimportantroleofheterogeneousglobaldnamethylationstatusontheprogressionoflungadenocarcinoma
AT yingjuwang analysisatthesinglecelllevelindicatesanimportantroleofheterogeneousglobaldnamethylationstatusontheprogressionoflungadenocarcinoma
AT xiaoningzhong analysisatthesinglecelllevelindicatesanimportantroleofheterogeneousglobaldnamethylationstatusontheprogressionoflungadenocarcinoma
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