Universität zu Köln

Franzen, Julia, Zirkel, Anne, Blake, Jonathon, Rath, Bjoern, Benes, Vladimir, Papantonis, Argyris ORCID: 0000-0001-7551-1073 and Wagner, Wolfgang ORCID: 0000-0002-1971-3217 (2017). Senescence-associated DNA methylation is stochastically acquired in subpopulations of mesenchymal stem cells. Aging Cell, 16 (1). S. 183 - 192. HOBOKEN: WILEY. ISSN 1474-9726

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Abstract

Replicative senescence has a major impact on function and integrity of cell preparations. This process is reflected by continuous DNA methylation (DNAm) changes at specific CpG dinucleotides in the course of in vitro culture, and such modifications can be used to estimate the state of cellular senescence for quality control of cell preparations. Still, it is unclear how senescence-associated DNAm changes are regulated and whether they occur simultaneously across a cell population. In this study, we analyzed global DNAm profiles of human mesenchymal stem cells (MSCs) and human umbilical vein endothelial cells (HUVECs) to demonstrate that senescence-associated DNAm changes are overall similar in these different cell types. Subsequently, an Epigenetic-Senescence-Signature, based on six CpGs, was either analyzed by pyrosequencing or by bar-coded bisulfite amplicon sequencing. There was a good correlation between predicted and real passage numbers in bulk populations of MSCs (R-2 = 0.67) and HUVECs (R-2 = 0.97). However, when we analyzed the Epigenetic-Senescence-Signature in subclones of MSCs, the predictions revealed high variation and they were not related to the adipogenic or osteogenic differentiation potential of the subclones. Notably, in clonally derived subpopulations, the DNAm levels of neighboring CpGs differed extensively, indicating that these genomic regions are not synchronously modified during senescence. Taken together, senescence-associated DNAm changes occur in a highly reproducible manner, but they are not synchronously co-regulated. They rather appear to be acquired stochastically-potentially evoked by other epigenetic modifications.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Franzen, Julia UNSPECIFIED UNSPECIFIED UNSPECIFIED Zirkel, Anne UNSPECIFIED UNSPECIFIED UNSPECIFIED Blake, Jonathon UNSPECIFIED UNSPECIFIED UNSPECIFIED Rath, Bjoern UNSPECIFIED UNSPECIFIED UNSPECIFIED Benes, Vladimir UNSPECIFIED UNSPECIFIED UNSPECIFIED Papantonis, Argyris UNSPECIFIED orcid.org/0000-0001-7551-1073 UNSPECIFIED Wagner, Wolfgang UNSPECIFIED orcid.org/0000-0002-1971-3217 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-241438
DOI:	10.1111/acel.12544
Journal or Publication Title:	Aging Cell
Volume:	16
Number:	1
Page Range:	S. 183 - 192
Date:	2017
Publisher:	WILEY
Place of Publication:	HOBOKEN
ISSN:	1474-9726
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language STROMAL CELLS; REPLICATIVE SENESCENCE; CELLULAR SENESCENCE; GENE-EXPRESSION; CPG SITES; CULTURE; CANCER; REORGANIZATION; LANDSCAPE; EXPANSION Multiple languages Cell Biology; Geriatrics & Gerontology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/24143