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Single-Cell Expression Variability Implies Cell Function

As single-cell RNA sequencing (scRNA-seq) data becomes widely available, cell-to-cell variability in gene expression, or single-cell expression variability (scEV), has been increasingly appreciated. However, it remains unclear whether this variability is functionally important and, if so, what are i...

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Autores principales: Osorio, Daniel, Yu, Xue, Zhong, Yan, Li, Guanxun, Serpedin, Erchin, Huang, Jianhua Z., Cai, James J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7017299/
https://www.ncbi.nlm.nih.gov/pubmed/31861624
http://dx.doi.org/10.3390/cells9010014
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author Osorio, Daniel
Yu, Xue
Zhong, Yan
Li, Guanxun
Serpedin, Erchin
Huang, Jianhua Z.
Cai, James J.
author_facet Osorio, Daniel
Yu, Xue
Zhong, Yan
Li, Guanxun
Serpedin, Erchin
Huang, Jianhua Z.
Cai, James J.
author_sort Osorio, Daniel
collection PubMed
description As single-cell RNA sequencing (scRNA-seq) data becomes widely available, cell-to-cell variability in gene expression, or single-cell expression variability (scEV), has been increasingly appreciated. However, it remains unclear whether this variability is functionally important and, if so, what are its implications for multi-cellular organisms. Here, we analyzed multiple scRNA-seq data sets from lymphoblastoid cell lines (LCLs), lung airway epithelial cells (LAECs), and dermal fibroblasts (DFs) and, for each cell type, selected a group of homogenous cells with highly similar expression profiles. We estimated the scEV levels for genes after correcting the mean-variance dependency in that data and identified 465, 466, and 364 highly variable genes (HVGs) in LCLs, LAECs, and DFs, respectively. Functions of these HVGs were found to be enriched with those biological processes precisely relevant to the corresponding cell type’s function, from which the scRNA-seq data used to identify HVGs were generated—e.g., cytokine signaling pathways were enriched in HVGs identified in LCLs, collagen formation in LAECs, and keratinization in DFs. We repeated the same analysis with scRNA-seq data from induced pluripotent stem cells (iPSCs) and identified only 79 HVGs with no statistically significant enriched functions; the overall scEV in iPSCs was of negligible magnitude. Our results support the “variation is function” hypothesis, arguing that scEV is required for cell type-specific, higher-level system function. Thus, quantifying and characterizing scEV are of importance for our understating of normal and pathological cellular processes.
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spelling pubmed-70172992020-02-28 Single-Cell Expression Variability Implies Cell Function Osorio, Daniel Yu, Xue Zhong, Yan Li, Guanxun Serpedin, Erchin Huang, Jianhua Z. Cai, James J. Cells Article As single-cell RNA sequencing (scRNA-seq) data becomes widely available, cell-to-cell variability in gene expression, or single-cell expression variability (scEV), has been increasingly appreciated. However, it remains unclear whether this variability is functionally important and, if so, what are its implications for multi-cellular organisms. Here, we analyzed multiple scRNA-seq data sets from lymphoblastoid cell lines (LCLs), lung airway epithelial cells (LAECs), and dermal fibroblasts (DFs) and, for each cell type, selected a group of homogenous cells with highly similar expression profiles. We estimated the scEV levels for genes after correcting the mean-variance dependency in that data and identified 465, 466, and 364 highly variable genes (HVGs) in LCLs, LAECs, and DFs, respectively. Functions of these HVGs were found to be enriched with those biological processes precisely relevant to the corresponding cell type’s function, from which the scRNA-seq data used to identify HVGs were generated—e.g., cytokine signaling pathways were enriched in HVGs identified in LCLs, collagen formation in LAECs, and keratinization in DFs. We repeated the same analysis with scRNA-seq data from induced pluripotent stem cells (iPSCs) and identified only 79 HVGs with no statistically significant enriched functions; the overall scEV in iPSCs was of negligible magnitude. Our results support the “variation is function” hypothesis, arguing that scEV is required for cell type-specific, higher-level system function. Thus, quantifying and characterizing scEV are of importance for our understating of normal and pathological cellular processes. MDPI 2019-12-19 /pmc/articles/PMC7017299/ /pubmed/31861624 http://dx.doi.org/10.3390/cells9010014 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Osorio, Daniel
Yu, Xue
Zhong, Yan
Li, Guanxun
Serpedin, Erchin
Huang, Jianhua Z.
Cai, James J.
Single-Cell Expression Variability Implies Cell Function
title Single-Cell Expression Variability Implies Cell Function
title_full Single-Cell Expression Variability Implies Cell Function
title_fullStr Single-Cell Expression Variability Implies Cell Function
title_full_unstemmed Single-Cell Expression Variability Implies Cell Function
title_short Single-Cell Expression Variability Implies Cell Function
title_sort single-cell expression variability implies cell function
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7017299/
https://www.ncbi.nlm.nih.gov/pubmed/31861624
http://dx.doi.org/10.3390/cells9010014
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