Epigenetic Classification of Human Mesenchymal Stromal Cells

Stem Cell Reports

Marcelo R.P. Ferreira¹  Ivan G. Costa¹  Martin Zenke²  Joana Frobel³  Julia Franzen³  Carola I. Weidner³  Danilo Candido de Almeida³  Wolfgang Wagner³ 

[1]Department of Cell Biology, IZKF Research Group Bioinformatics, Institute for Biomedical Engineering, RWTH Aachen University Medical School, 52074 Aachen, Germany

[2]Department of Cell Biology, Institute for Biomedical Engineering, RWTH Aachen University Medical School, 52074 Aachen, Germany

[3]Division of Stem Cell Biology and Cellular Engineering, Helmholtz-Institute for Biomedical Engineering, RWTH Aachen University Medical School, Pauwelsstraße 20, 52074 Aachen, Germany

关键词: epigenetic score;    mesenchymal stromal cell;    mesenchymal stem cell;    fibroblast;    bone marrow;    adipose tissue;    DNA methylation;   

DOI  :  10.1016/j.stemcr.2016.01.003

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown