Age-associated hydroxymethylation in human bone-marrow mesenchymal stem cells

Estela G. Toraño, Gustavo F. Bayón, Álvaro del Real, Marta I. Sierra, María G. García, Antonella Carella, Thalia Belmonte, Rocío G. Urdinguio, Isabel Cubillo, Javier García-Castro, Jesus Delgado-Calle, Flor M. Pérez-Campo, José A. Riancho, Mario F. Fraga, Agustín F. Fernández

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Background: Age-associated changes in genomic DNA methylation have been primarily attributed to 5-methylcytosine (5mC). However, the recent discovery of 5-hydroxymethylcytosine (5hmC) suggests that this epigenetic mark might also play a role in the process. Methods: Here, we analyzed the genome-wide profile of 5hmc in mesenchymal stem cells (MSCs) obtained from bone-marrow donors, aged 2-89 years. Results: We identified 10,685 frequently hydroxymethylated CpG sites in MSCs that were, as in other cell types, significantly associated with low density CpG regions, introns, the histone posttranslational modification H3k4me1 and enhancers. Study of the age-associated changes to 5hmC identified 785 hyper- and 846 hypo-hydroxymethylated CpG sites in the MSCs obtained from older individuals. Conclusions: DNA hyper-hydroxymethylation in the advanced-age group was associated with loss of 5mC, which suggests that, at specific CpG sites, this epigenetic modification might play a role in DNA methylation changes during lifetime. Since bone-marrow MSCs have many clinical applications, and the fact that the epigenomic alterations in this cell type associated with aging identified in this study could have associated functional effects, the age of donors should be taken into account in clinical settings.

Original languageEnglish (US)
Article number207
JournalJournal of Translational Medicine
Volume14
Issue number1
DOIs
StatePublished - 2016
Externally publishedYes

Fingerprint

Stem cells
Mesenchymal Stromal Cells
Bone
Bone Marrow
Epigenomics
5-Methylcytosine
DNA Methylation
Histone Code
Tissue Donors
Post Translational Protein Processing
Histones
Introns
Age Groups
Genes
Aging of materials
Genome
DNA
5-hydroxymethylcytosine

Keywords

  • 5hmC
  • Aging
  • Bone-marrow
  • Epigenetics
  • MSCs

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Toraño, E. G., Bayón, G. F., del Real, Á., Sierra, M. I., García, M. G., Carella, A., ... Fernández, A. F. (2016). Age-associated hydroxymethylation in human bone-marrow mesenchymal stem cells. Journal of Translational Medicine, 14(1), [207]. https://doi.org/10.1186/s12967-016-0966-x

Age-associated hydroxymethylation in human bone-marrow mesenchymal stem cells. / Toraño, Estela G.; Bayón, Gustavo F.; del Real, Álvaro; Sierra, Marta I.; García, María G.; Carella, Antonella; Belmonte, Thalia; Urdinguio, Rocío G.; Cubillo, Isabel; García-Castro, Javier; Delgado-Calle, Jesus; Pérez-Campo, Flor M.; Riancho, José A.; Fraga, Mario F.; Fernández, Agustín F.

In: Journal of Translational Medicine, Vol. 14, No. 1, 207, 2016.

Research output: Contribution to journalArticle

Toraño, EG, Bayón, GF, del Real, Á, Sierra, MI, García, MG, Carella, A, Belmonte, T, Urdinguio, RG, Cubillo, I, García-Castro, J, Delgado-Calle, J, Pérez-Campo, FM, Riancho, JA, Fraga, MF & Fernández, AF 2016, 'Age-associated hydroxymethylation in human bone-marrow mesenchymal stem cells', Journal of Translational Medicine, vol. 14, no. 1, 207. https://doi.org/10.1186/s12967-016-0966-x
Toraño, Estela G. ; Bayón, Gustavo F. ; del Real, Álvaro ; Sierra, Marta I. ; García, María G. ; Carella, Antonella ; Belmonte, Thalia ; Urdinguio, Rocío G. ; Cubillo, Isabel ; García-Castro, Javier ; Delgado-Calle, Jesus ; Pérez-Campo, Flor M. ; Riancho, José A. ; Fraga, Mario F. ; Fernández, Agustín F. / Age-associated hydroxymethylation in human bone-marrow mesenchymal stem cells. In: Journal of Translational Medicine. 2016 ; Vol. 14, No. 1.
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abstract = "Background: Age-associated changes in genomic DNA methylation have been primarily attributed to 5-methylcytosine (5mC). However, the recent discovery of 5-hydroxymethylcytosine (5hmC) suggests that this epigenetic mark might also play a role in the process. Methods: Here, we analyzed the genome-wide profile of 5hmc in mesenchymal stem cells (MSCs) obtained from bone-marrow donors, aged 2-89 years. Results: We identified 10,685 frequently hydroxymethylated CpG sites in MSCs that were, as in other cell types, significantly associated with low density CpG regions, introns, the histone posttranslational modification H3k4me1 and enhancers. Study of the age-associated changes to 5hmC identified 785 hyper- and 846 hypo-hydroxymethylated CpG sites in the MSCs obtained from older individuals. Conclusions: DNA hyper-hydroxymethylation in the advanced-age group was associated with loss of 5mC, which suggests that, at specific CpG sites, this epigenetic modification might play a role in DNA methylation changes during lifetime. Since bone-marrow MSCs have many clinical applications, and the fact that the epigenomic alterations in this cell type associated with aging identified in this study could have associated functional effects, the age of donors should be taken into account in clinical settings.",
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AU - Toraño, Estela G.

AU - Bayón, Gustavo F.

AU - del Real, Álvaro

AU - Sierra, Marta I.

AU - García, María G.

AU - Carella, Antonella

AU - Belmonte, Thalia

AU - Urdinguio, Rocío G.

AU - Cubillo, Isabel

AU - García-Castro, Javier

AU - Delgado-Calle, Jesus

AU - Pérez-Campo, Flor M.

AU - Riancho, José A.

AU - Fraga, Mario F.

AU - Fernández, Agustín F.

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N2 - Background: Age-associated changes in genomic DNA methylation have been primarily attributed to 5-methylcytosine (5mC). However, the recent discovery of 5-hydroxymethylcytosine (5hmC) suggests that this epigenetic mark might also play a role in the process. Methods: Here, we analyzed the genome-wide profile of 5hmc in mesenchymal stem cells (MSCs) obtained from bone-marrow donors, aged 2-89 years. Results: We identified 10,685 frequently hydroxymethylated CpG sites in MSCs that were, as in other cell types, significantly associated with low density CpG regions, introns, the histone posttranslational modification H3k4me1 and enhancers. Study of the age-associated changes to 5hmC identified 785 hyper- and 846 hypo-hydroxymethylated CpG sites in the MSCs obtained from older individuals. Conclusions: DNA hyper-hydroxymethylation in the advanced-age group was associated with loss of 5mC, which suggests that, at specific CpG sites, this epigenetic modification might play a role in DNA methylation changes during lifetime. Since bone-marrow MSCs have many clinical applications, and the fact that the epigenomic alterations in this cell type associated with aging identified in this study could have associated functional effects, the age of donors should be taken into account in clinical settings.

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