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Single-cell analysis reveals early manifestation of cancerous phenotype in pre-malignant esophageal cells. PLoS One 2013;8(10):e75365

Date

10/12/2013

Pubmed ID

24116039

Pubmed Central ID

PMC3792915

DOI

10.1371/journal.pone.0075365

Abstract

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.

Author List

Wang J, Shi X, Johnson RH, Kelbauskas L, Zhang W, Meldrum DR

Author

Roger H. Johnson PhD Associate Professor in the Biophysics department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Adenocarcinoma
Barrett Esophagus
Cell Line
DNA, Mitochondrial
Disease Progression
Epithelial Cells
Esophageal Neoplasms
Esophagus
Humans
Membrane Potential, Mitochondrial
Mitochondria
Phenotype
Single-Cell Analysis