Single-cell analysis reveals early manifestation of cancerous phenotype in pre-malignant esophageal cells.

Cellular heterogeneity plays a pivotal role in a variety of functional processes in vivo including carcinogenesis. However, our knowledge about cell-to-cell diversity and how differences in individual cells manifest in alterations at the population level remains very limited mainly due to the lack o...

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Autores principales:	Jiangxin Wang, Xu Shi, Roger H Johnson, Laimonas Kelbauskas, Weiwen Zhang, Deirdre R Meldrum
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/476dc4e1f2cc428494d89b53d1668589
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spelling	oai:doaj.org-article:476dc4e1f2cc428494d89b53d16685892021-11-18T08:51:57ZSingle-cell analysis reveals early manifestation of cancerous phenotype in pre-malignant esophageal cells.1932-620310.1371/journal.pone.0075365https://doaj.org/article/476dc4e1f2cc428494d89b53d16685892013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24116039/?tool=EBIhttps://doaj.org/toc/1932-6203Cellular heterogeneity plays a pivotal role in a variety of functional processes in vivo including carcinogenesis. However, our knowledge about cell-to-cell diversity and how differences in individual cells manifest in alterations at the population level remains very limited mainly due to the lack of appropriate tools enabling studies at the single-cell level. We present a study on changes in cellular heterogeneity in the context of pre-malignant progression in response to hypoxic stress. Utilizing pre-malignant progression of Barrett's esophagus (BE) as a disease model system we studied molecular mechanisms underlying the progression from metaplastic to dysplastic (pre-cancerous) stage. We used newly developed methods enabling measurements of cell-to-cell differences in copy numbers of mitochondrial DNA, expression levels of a set of mitochondrial and nuclear genes involved in hypoxia response pathways, and mitochondrial membrane potential. In contrast to bulk cell studies reported earlier, our study shows significant differences between metaplastic and dysplastic BE cells in both average values and single-cell parameter distributions of mtDNA copy numbers, mitochondrial function, and mRNA expression levels of studied genes. Based on single-cell data analysis, we propose that mitochondria may be one of the key factors in pre-malignant progression in BE.Jiangxin WangXu ShiRoger H JohnsonLaimonas KelbauskasWeiwen ZhangDeirdre R MeldrumPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 10, p e75365 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jiangxin Wang Xu Shi Roger H Johnson Laimonas Kelbauskas Weiwen Zhang Deirdre R Meldrum Single-cell analysis reveals early manifestation of cancerous phenotype in pre-malignant esophageal cells.
description	Cellular heterogeneity plays a pivotal role in a variety of functional processes in vivo including carcinogenesis. However, our knowledge about cell-to-cell diversity and how differences in individual cells manifest in alterations at the population level remains very limited mainly due to the lack of appropriate tools enabling studies at the single-cell level. We present a study on changes in cellular heterogeneity in the context of pre-malignant progression in response to hypoxic stress. Utilizing pre-malignant progression of Barrett's esophagus (BE) as a disease model system we studied molecular mechanisms underlying the progression from metaplastic to dysplastic (pre-cancerous) stage. We used newly developed methods enabling measurements of cell-to-cell differences in copy numbers of mitochondrial DNA, expression levels of a set of mitochondrial and nuclear genes involved in hypoxia response pathways, and mitochondrial membrane potential. In contrast to bulk cell studies reported earlier, our study shows significant differences between metaplastic and dysplastic BE cells in both average values and single-cell parameter distributions of mtDNA copy numbers, mitochondrial function, and mRNA expression levels of studied genes. Based on single-cell data analysis, we propose that mitochondria may be one of the key factors in pre-malignant progression in BE.
format	article
author	Jiangxin Wang Xu Shi Roger H Johnson Laimonas Kelbauskas Weiwen Zhang Deirdre R Meldrum
author_facet	Jiangxin Wang Xu Shi Roger H Johnson Laimonas Kelbauskas Weiwen Zhang Deirdre R Meldrum
author_sort	Jiangxin Wang
title	Single-cell analysis reveals early manifestation of cancerous phenotype in pre-malignant esophageal cells.
title_short	Single-cell analysis reveals early manifestation of cancerous phenotype in pre-malignant esophageal cells.
title_full	Single-cell analysis reveals early manifestation of cancerous phenotype in pre-malignant esophageal cells.
title_fullStr	Single-cell analysis reveals early manifestation of cancerous phenotype in pre-malignant esophageal cells.
title_full_unstemmed	Single-cell analysis reveals early manifestation of cancerous phenotype in pre-malignant esophageal cells.
title_sort	single-cell analysis reveals early manifestation of cancerous phenotype in pre-malignant esophageal cells.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/476dc4e1f2cc428494d89b53d1668589
work_keys_str_mv	AT jiangxinwang singlecellanalysisrevealsearlymanifestationofcancerousphenotypeinpremalignantesophagealcells AT xushi singlecellanalysisrevealsearlymanifestationofcancerousphenotypeinpremalignantesophagealcells AT rogerhjohnson singlecellanalysisrevealsearlymanifestationofcancerousphenotypeinpremalignantesophagealcells AT laimonaskelbauskas singlecellanalysisrevealsearlymanifestationofcancerousphenotypeinpremalignantesophagealcells AT weiwenzhang singlecellanalysisrevealsearlymanifestationofcancerousphenotypeinpremalignantesophagealcells AT deirdrermeldrum singlecellanalysisrevealsearlymanifestationofcancerousphenotypeinpremalignantesophagealcells
_version_	1718421197719339008

Single-cell analysis reveals early manifestation of cancerous phenotype in pre-malignant esophageal cells.

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