Project description:Human induced pluripotent stem cells (iPSCs) - derived mesenchymal stromal cells (iMSCs) are a potentially useful cell type for circumventing ageing-related shortfalls associated with primary mesenchymal or skeletal stromal cells (MSCs/SSCs). To date, the extent of the reflection of ageing-hallmarks in iMSCs differentiated from iPSCs derived from elderly donors remains unclear. In this study, we show that fetal (55 days post conception) femur-derived MSCs and MSCs isolated from aged (60 – 74 years) donors differ in their transcriptome and secretome profile. Yet, iMSCs irrespective of donor age and cell type acquired a rejuvenation gene signature, specifically, INHBE, DNMT3B, POU5F1P1, CDKN1C, GCNT2; also present in pluripotent stem cells but not observed in the parental MSCs. Furthermore, dendrograms generated from the transcriptomes of iMSCs derived from the human embryonic stem cell line H1, fetal and aged MSCs always clustered together with the parental fetal femur-derived MSCs. In addition, these were distinct from MSCs isolated from aged donors when comparing gene ontologies (GOs) related to ageing processes. Critically, in terms of regenerative medicine applications, iMSCs re-acquired a similar secretome (e.g. SERPINE1, SDF-1a, HGF, IL6, IL10, THBS1) to that of the parental fetal MSCs, thus re-enforcing their capabilities of imparting context dependent paracrine signaling.
Project description:To examine underlying differences in gene expression between young and old MSCs and the effects of exposure of old MSCs to media conditioned by young MSCs on gene expression we performed RNA sequencing
Project description:Proliferative and replicative senescent fibroblasts from aged human donors were reprogrammed towards pluripotency and re-differentiated in fibroblasts and then further analyzed for rejuvenation assessment. Comparison of microarrays were performed by non hierarchical clustering visualized in with Treeview software
Project description:Proliferative and replicative senescent fibroblasts from aged human donors were reprogrammed towards pluripotency and re-differentiated in fibroblasts and then further analyzed for rejuvenation assessment.
Project description:Aging is associated with a progressive decline in cellular function. To reset the aged cellular phenotype, various reprogramming approaches, including mechanical routes, have been proposed. However, the epigenetic mechanisms underlying cellular rejuvenation are poorly understood. We studied the transcriptional changes in young, aged and mechanically rejuvenated fibroblasts using RNA-seq. The mechanically rejuvenated aged fibroblasts, that had reset their transcription to a younger cell state. In addition, the rejuvenated cells contractile properties were maintained over multiple cell passages. Taken together, our results provide a multi-scale characterization of the chromatin reorganization that accompanies cellular aging and rejuvenation.
Project description:This SuperSeries is composed of the following subset Series: GSE25068: PcG/TrxG profiling of differentially aged adipose-derived mesenchymal stem cells GSE25069: Whole-genome microarray of long-term cultured adipose derived mesenchymal stem cells from differentially-aged mice GSE25679: microRNA profiling of mesenchymal stem cells from adipose tissue of differentially aged mice Refer to individual Series
Project description:De novo DNA methylation establishes T cell exhaustion and inhibits PD-1 blockade-mediated T-cell rejuvenation. Expression profiling of chronically stimulated WT and Dnmt3a cKO antigen-specific CD8 T cells.
Project description:Aging is associated with a progressive decline in cellular function. To reset the aged cellular phenotype, various reprogramming approaches, including mechanical routes, have been proposed. However, the epigenetic mechanisms underlying cellular rejuvenation are poorly understood. We studied the transcriptional and genome-wide chromatin organization changes in young, aged and mechanically rejuvenated fibroblasts using RNA-seq and Hi-C experiments. The mechanically rejuvenated aged fibroblasts, that had reset their transcription to a younger cell state, showed a reorganization of the inter-chromosomal contacts and lamina-associated domains. Interestingly, the observed chromatin reorganization correlated with the transcriptional changes. Immunofluorescence experiments in the rejuvenated state confirmed increased contractility and reduced chromosome copy number variations, similar to younger fibroblasts. In addition, the rejuvenated contractile properties were maintained over multiple cell passages. Taken together, our results provide a multi-scale characterization of the chromatin reorganization that accompanies cellular aging and rejuvenation.