Epigenetic Classification of Human Mesenchymal Stromal Cells

Standardization of mesenchymal stromal cells (MSCs) is hampered by the lack of a precise definition for these cell preparations; for example, there are no molecular markers to discern MSCs and fibroblasts. In this study, we followed the hypothesis that specific DNA methylation (DNAm) patterns can as...

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Main Authors: de Almeida, Danilo Candido, Ferreira, Marcelo R.P., Franzen, Julia, Weidner, Carola I., Frobel, Joana, Zenke, Martin, Costa, Ivan G., Wagner, Wolfgang
Format: Online
Language:English
Published: Elsevier 2016
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4750140/
id pubmed-4750140
recordtype oai_dc
spelling pubmed-47501402016-03-02 Epigenetic Classification of Human Mesenchymal Stromal Cells de Almeida, Danilo Candido Ferreira, Marcelo R.P. Franzen, Julia Weidner, Carola I. Frobel, Joana Zenke, Martin Costa, Ivan G. Wagner, Wolfgang Report Standardization of mesenchymal stromal cells (MSCs) is hampered by the lack of a precise definition for these cell preparations; for example, there are no molecular markers to discern MSCs and fibroblasts. In this study, we followed the hypothesis that specific DNA methylation (DNAm) patterns can assist classification of MSCs. We utilized 190 DNAm profiles to address the impact of tissue of origin, donor age, replicative senescence, and serum supplements on the epigenetic makeup. Based on this, we elaborated a simple epigenetic signature based on two CpG sites to classify MSCs and fibroblasts, referred to as the Epi-MSC-Score. Another two-CpG signature can distinguish between MSCs from bone marrow and adipose tissue, referred to as the Epi-Tissue-Score. These assays were validated by site-specific pyrosequencing analysis in 34 primary cell preparations. Furthermore, even individual subclones of MSCs were correctly classified by our epigenetic signatures. In summary, we propose an alternative concept to use DNAm patterns for molecular definition of cell preparations, and our epigenetic scores facilitate robust and cost-effective quality control of MSC cultures. Elsevier 2016-02-09 /pmc/articles/PMC4750140/ /pubmed/26862701 http://dx.doi.org/10.1016/j.stemcr.2016.01.003 Text en © 2016 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author de Almeida, Danilo Candido
Ferreira, Marcelo R.P.
Franzen, Julia
Weidner, Carola I.
Frobel, Joana
Zenke, Martin
Costa, Ivan G.
Wagner, Wolfgang
spellingShingle de Almeida, Danilo Candido
Ferreira, Marcelo R.P.
Franzen, Julia
Weidner, Carola I.
Frobel, Joana
Zenke, Martin
Costa, Ivan G.
Wagner, Wolfgang
Epigenetic Classification of Human Mesenchymal Stromal Cells
author_facet de Almeida, Danilo Candido
Ferreira, Marcelo R.P.
Franzen, Julia
Weidner, Carola I.
Frobel, Joana
Zenke, Martin
Costa, Ivan G.
Wagner, Wolfgang
author_sort de Almeida, Danilo Candido
title Epigenetic Classification of Human Mesenchymal Stromal Cells
title_short Epigenetic Classification of Human Mesenchymal Stromal Cells
title_full Epigenetic Classification of Human Mesenchymal Stromal Cells
title_fullStr Epigenetic Classification of Human Mesenchymal Stromal Cells
title_full_unstemmed Epigenetic Classification of Human Mesenchymal Stromal Cells
title_sort epigenetic classification of human mesenchymal stromal cells
description Standardization of mesenchymal stromal cells (MSCs) is hampered by the lack of a precise definition for these cell preparations; for example, there are no molecular markers to discern MSCs and fibroblasts. In this study, we followed the hypothesis that specific DNA methylation (DNAm) patterns can assist classification of MSCs. We utilized 190 DNAm profiles to address the impact of tissue of origin, donor age, replicative senescence, and serum supplements on the epigenetic makeup. Based on this, we elaborated a simple epigenetic signature based on two CpG sites to classify MSCs and fibroblasts, referred to as the Epi-MSC-Score. Another two-CpG signature can distinguish between MSCs from bone marrow and adipose tissue, referred to as the Epi-Tissue-Score. These assays were validated by site-specific pyrosequencing analysis in 34 primary cell preparations. Furthermore, even individual subclones of MSCs were correctly classified by our epigenetic signatures. In summary, we propose an alternative concept to use DNAm patterns for molecular definition of cell preparations, and our epigenetic scores facilitate robust and cost-effective quality control of MSC cultures.
publisher Elsevier
publishDate 2016
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4750140/
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