Age-related changes in mesenchymal stem cells identified using a multi-omics approach
Mesenchymal stem cells (MSC) are capable of multipotent differentiation into connective tissues and as such are an attractive source for autologous cell-based treatments for many clinical diseases and injuries. Ageing is associated with various altered cellular phenotypes coupled with a variety of t...
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AO Research Institute Davos
2016
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ftdoajarticles:oai:doaj.org/article:f205479493c5441384ae1059717f7466 2023-05-15T16:01:36+02:00 Age-related changes in mesenchymal stem cells identified using a multi-omics approach MJ Peffers J Collins Y Fang K Goljanek-Whysall M Rushton J Loughlin C Proctor PD Clegg 2016-02-01T00:00:00Z https://doi.org/10.22203/eCM.v031a10 https://doaj.org/article/f205479493c5441384ae1059717f7466 EN eng AO Research Institute Davos http://www.ecmjournal.org/papers/vol031/pdf/v031a10.pdf https://doaj.org/toc/1473-2262 doi:10.22203/eCM.v031a10 1473-2262 https://doaj.org/article/f205479493c5441384ae1059717f7466 European Cells & Materials, Vol 31, Pp 136-159 (2016) Mesenchymal stem cells RNAseq epigenetics proteomics ageing Surgery RD1-811 Diseases of the musculoskeletal system RC925-935 article 2016 ftdoajarticles https://doi.org/10.22203/eCM.v031a10 2022-12-31T07:08:45Z Mesenchymal stem cells (MSC) are capable of multipotent differentiation into connective tissues and as such are an attractive source for autologous cell-based treatments for many clinical diseases and injuries. Ageing is associated with various altered cellular phenotypes coupled with a variety of transcriptional, epigenetic and translational changes. Furthermore, the regeneration potential of MSCs is reduced with increasing age and is correlated with changes in cellular functions. This study used a systems biology approach to investigate the transcriptomic (RNASeq), epigenetic (miRNASeq and DNA methylation) and protein alterations in ageing MSCs in order to understand the age-related functional and biological variations, which may affect their applications to regenerative medicine. We identified no change in expression of the cellular senescence markers. Alterations were evident at both the transcriptional and post-transcriptional level in a number of transcription factors. There was enrichment in genes involved in developmental disorders at mRNA and differential methylated loci (DML) level. Alterations in energy metabolism were apparent at the DML and protein level. The microRNA miR-199b-5p, whose expression was reduced in old MSCs, had predicted gene targets involved in energy metabolism and cell survival. Additionally, enrichment of DML and proteins in cell survival was evident. Enrichment in metabolic processes was revealed at the protein level and in genes identified as undergoing alternate splicing. Overall, an altered phenotype in MSC ageing at a number of levels implicated roles for inflamm-ageing and mitochondrial ageing. Identified changes represent novel insights into the ageing process, with implications for stem cell therapies in older patients. Article in Journal/Newspaper DML Directory of Open Access Journals: DOAJ Articles European Cells and Materials 31 136 159 |
institution |
Open Polar |
collection |
Directory of Open Access Journals: DOAJ Articles |
op_collection_id |
ftdoajarticles |
language |
English |
topic |
Mesenchymal stem cells RNAseq epigenetics proteomics ageing Surgery RD1-811 Diseases of the musculoskeletal system RC925-935 |
spellingShingle |
Mesenchymal stem cells RNAseq epigenetics proteomics ageing Surgery RD1-811 Diseases of the musculoskeletal system RC925-935 MJ Peffers J Collins Y Fang K Goljanek-Whysall M Rushton J Loughlin C Proctor PD Clegg Age-related changes in mesenchymal stem cells identified using a multi-omics approach |
topic_facet |
Mesenchymal stem cells RNAseq epigenetics proteomics ageing Surgery RD1-811 Diseases of the musculoskeletal system RC925-935 |
description |
Mesenchymal stem cells (MSC) are capable of multipotent differentiation into connective tissues and as such are an attractive source for autologous cell-based treatments for many clinical diseases and injuries. Ageing is associated with various altered cellular phenotypes coupled with a variety of transcriptional, epigenetic and translational changes. Furthermore, the regeneration potential of MSCs is reduced with increasing age and is correlated with changes in cellular functions. This study used a systems biology approach to investigate the transcriptomic (RNASeq), epigenetic (miRNASeq and DNA methylation) and protein alterations in ageing MSCs in order to understand the age-related functional and biological variations, which may affect their applications to regenerative medicine. We identified no change in expression of the cellular senescence markers. Alterations were evident at both the transcriptional and post-transcriptional level in a number of transcription factors. There was enrichment in genes involved in developmental disorders at mRNA and differential methylated loci (DML) level. Alterations in energy metabolism were apparent at the DML and protein level. The microRNA miR-199b-5p, whose expression was reduced in old MSCs, had predicted gene targets involved in energy metabolism and cell survival. Additionally, enrichment of DML and proteins in cell survival was evident. Enrichment in metabolic processes was revealed at the protein level and in genes identified as undergoing alternate splicing. Overall, an altered phenotype in MSC ageing at a number of levels implicated roles for inflamm-ageing and mitochondrial ageing. Identified changes represent novel insights into the ageing process, with implications for stem cell therapies in older patients. |
format |
Article in Journal/Newspaper |
author |
MJ Peffers J Collins Y Fang K Goljanek-Whysall M Rushton J Loughlin C Proctor PD Clegg |
author_facet |
MJ Peffers J Collins Y Fang K Goljanek-Whysall M Rushton J Loughlin C Proctor PD Clegg |
author_sort |
MJ Peffers |
title |
Age-related changes in mesenchymal stem cells identified using a multi-omics approach |
title_short |
Age-related changes in mesenchymal stem cells identified using a multi-omics approach |
title_full |
Age-related changes in mesenchymal stem cells identified using a multi-omics approach |
title_fullStr |
Age-related changes in mesenchymal stem cells identified using a multi-omics approach |
title_full_unstemmed |
Age-related changes in mesenchymal stem cells identified using a multi-omics approach |
title_sort |
age-related changes in mesenchymal stem cells identified using a multi-omics approach |
publisher |
AO Research Institute Davos |
publishDate |
2016 |
url |
https://doi.org/10.22203/eCM.v031a10 https://doaj.org/article/f205479493c5441384ae1059717f7466 |
genre |
DML |
genre_facet |
DML |
op_source |
European Cells & Materials, Vol 31, Pp 136-159 (2016) |
op_relation |
http://www.ecmjournal.org/papers/vol031/pdf/v031a10.pdf https://doaj.org/toc/1473-2262 doi:10.22203/eCM.v031a10 1473-2262 https://doaj.org/article/f205479493c5441384ae1059717f7466 |
op_doi |
https://doi.org/10.22203/eCM.v031a10 |
container_title |
European Cells and Materials |
container_volume |
31 |
container_start_page |
136 |
op_container_end_page |
159 |
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1766397389035274240 |