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Series GSE65172 Query DataSets for GSE65172
Status Public on Jul 01, 2015
Title NF-κB activation impairs somatic cell reprogramming in ageing [MSCs]
Organism Homo sapiens
Experiment type Expression profiling by array
Summary Transcriptional profiling of human control and Néstor-Guillermo Progeria Syndrome (NGPS) mesenchymal stem cells (MSCs).

Somatic cell reprogramming involves rejuvenation of adult cells and relies on the ability to erase age-associated molecular marks. Accordingly, reprogramming efficiency declines with ageing, and age-associated features such as genetic instability, cell senescence or telomere shortening negatively affect this process. However, the regulatory mechanisms that constitute age-associated barriers for cell reprogramming remain largely unknown. Here, by using cells from patients with premature ageing, we demonstrate that NF-κB activation is a critical barrier for the generation of induced pluripotent stem cells (iPSCs) in ageing. We show that NF-κB repression occurs during cell reprogramming towards a pluripotent state. Conversely, ageing-associated NF-κB hyperactivation impairs generation of iPSCs by eliciting reprogramming repressors DOT1L and YY1, reinforcing cell senescence signals and down-regulating pluripotency genes. We also show that genetic and pharmacological NF-κB inhibitory strategies significantly increase the reprogramming efficiency of fibroblasts from Néstor-Guillermo Progeria Syndrome (NGPS) and Hutchinson-Gilford Progeria Syndrome (HGPS) patients, as well as from normal aged donors. Finally, we demonstrate that DOT1L inhibition in vivo ameliorates the accelerated ageing phenotype and extends lifespan in a progeroid animal model. Collectively, our results provide evidence for a novel role of NF-κB in the control of cell fate transitions and reinforce the interest of studying age-associated molecular impairments to implement cell reprogramming methodologies, and to identify new targets of rejuvenation strategies.
 
Overall design Control and NGPS MSCs were differentiated into bone in the presence or absence of sodium salicylate. Total RNA was extracted and global gene expression was analyzed.
 
Contributor(s) Osorio FG, Soria-Valles C, Freije JM, Lopez-Otin C
Citation(s) 26214134
Submission date Jan 21, 2015
Last update date Jul 26, 2018
Contact name Jose M.P. Freije
E-mail(s) jmpf@uniovi.es
Phone 34-985106281
Organization name Universidad de Oviedo
Department Bioquimica y Biologia Molecular
Lab IUOPA
Street address C/ Fernando Bongera s/n
City Oviedo
State/province Asturias
ZIP/Postal code 33006
Country Spain
 
Platforms (1)
GPL6244 [HuGene-1_0-st] Affymetrix Human Gene 1.0 ST Array [transcript (gene) version]
Samples (6)
GSM1588589 Control MSCs
GSM1588590 NaS Control MSCs
GSM1588591 NGPS-NI MSCs
This SubSeries is part of SuperSeries:
GSE65173 NF-κB activation impairs somatic cell reprogramming in ageing
Relations
BioProject PRJNA273329

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE65172_RAW.tar 26.6 Mb (http)(custom) TAR (of CEL)
Processed data included within Sample table

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