Replicative senescence is associated with nuclear reorganization and DNA methylation at specific transcription factor binding sites (RNA-seq)

Primary cells enter replicative senescence after a limited number of cell divisions. This process is associated with reproducible changes in DNA methylation (DNAm) at specific sites in the genome. The mechanism that drives senescence-associated DNAm changes remains unknown and may arise through drift in DNAm or through regulated, senescence dependent modifications at specific sites in the genome. In this study, we analyzed the reorganization of nuclear architecture and DNA methylation during long-term culture of human fibroblasts and mesenchymal stromal cells (MSCs). [RNA-seq] Overall design: RNA was isolated from 1,000,000 cells of three MSC donors (59, 64, and 73 years old) at passage 4 and passage 13 using the miRNeasy Mini Kit (Qiagen). Gene expression profiles were analzyed by deep sequencing with IlluminaHiSeq 2000 technology with a read length of 50 bases at EMBL gene core facility (Heidelberg, Germany).

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Hänzelmann S, Beier F, Gusmao EG, Koch CM, Hummel S, Charapitsa I, Joussen S, Benes V, Brümmendorf TH, Reid G, Costa IG, Wagner W