Adult adipose tissue-derived mesenchymal stem cells (ASCs) constitute a vital population of multipotent cells capable of differentiating into numerous end-organ phenotypes. However, scientific and translational endeavors to harness the regenerative potential of ASCs are currently limited by an incomplete understanding of the mechanisms that determine cell-lineage commitment and stemness. In the current study, we used reduced representation bisulfite sequencing (RRBS) analysis to identify epigenetic gene targets and cellular processes that are responsive to 50-azacitidine (50- AZA). We describe specific changes to DNA methylation of ASCs, uncovering pathways likely associated with the enhancement of their proliferative capacity. We identified 4,797 differentially methylated regions (FDR < 0.05) associated with 3,625 genes, of which 1,584 DMRs annotated to the promoter region. Gene set enrichment of differentially methylated promoters identified “phagocytosis,” “type 2 diabetes,” and “metabolic pathways” as disproportionately hypomethylated, whereas “adipocyte differentiation” was the most-enriched pathway among hyper-methylated gene promoters. Weighted coexpression network analysis of DMRs identified clusters associated with cellular proliferation and other developmental programs. Furthermore, the ELK4 binding site was disproportionately hyper-methylated within the promoters of genes associated with AKT signaling. Overall, this study offers numerous preliminary insights into the epigenetic landscape that influences the regenerative capacity of human ASCs.

Differential DNA methylation encodes proliferation and senescence programs in human adipose-derived mesenchymal stem cells / Pepin, Mark E.; Infante, Teresa; Benincasa, Giuditta; Schiano, Concetta; Miceli, Marco; Ceccarelli, Simona; Megiorni, Francesca; Anastasiadou, Eleni; Della Valle, Giovanni; Fatone, Gerardo; Faenza, Mario; Docimo, Ludovico; Nicoletti, Giovanni F.; Marchese, Cinzia; Wende, Adam R.; Napoli., Claudio. - In: FRONTIERS IN GENETICS. - ISSN 1664-8021. - 11:11(2020). [10.3389/fgene.2020.00346]

Differential DNA methylation encodes proliferation and senescence programs in human adipose-derived mesenchymal stem cells

Simona Ceccarelli;Francesca Megiorni;Eleni Anastasiadou;Cinzia Marchese;
2020

Abstract

Adult adipose tissue-derived mesenchymal stem cells (ASCs) constitute a vital population of multipotent cells capable of differentiating into numerous end-organ phenotypes. However, scientific and translational endeavors to harness the regenerative potential of ASCs are currently limited by an incomplete understanding of the mechanisms that determine cell-lineage commitment and stemness. In the current study, we used reduced representation bisulfite sequencing (RRBS) analysis to identify epigenetic gene targets and cellular processes that are responsive to 50-azacitidine (50- AZA). We describe specific changes to DNA methylation of ASCs, uncovering pathways likely associated with the enhancement of their proliferative capacity. We identified 4,797 differentially methylated regions (FDR < 0.05) associated with 3,625 genes, of which 1,584 DMRs annotated to the promoter region. Gene set enrichment of differentially methylated promoters identified “phagocytosis,” “type 2 diabetes,” and “metabolic pathways” as disproportionately hypomethylated, whereas “adipocyte differentiation” was the most-enriched pathway among hyper-methylated gene promoters. Weighted coexpression network analysis of DMRs identified clusters associated with cellular proliferation and other developmental programs. Furthermore, the ELK4 binding site was disproportionately hyper-methylated within the promoters of genes associated with AKT signaling. Overall, this study offers numerous preliminary insights into the epigenetic landscape that influences the regenerative capacity of human ASCs.
whole-genome DNA methylation; stem cell biology; regenerative medicine; computational biology; 50-azacitidine; epigenomics and epigenetics; cellular reprogramming
01 Pubblicazione su rivista::01a Articolo in rivista
Differential DNA methylation encodes proliferation and senescence programs in human adipose-derived mesenchymal stem cells / Pepin, Mark E.; Infante, Teresa; Benincasa, Giuditta; Schiano, Concetta; Miceli, Marco; Ceccarelli, Simona; Megiorni, Francesca; Anastasiadou, Eleni; Della Valle, Giovanni; Fatone, Gerardo; Faenza, Mario; Docimo, Ludovico; Nicoletti, Giovanni F.; Marchese, Cinzia; Wende, Adam R.; Napoli., Claudio. - In: FRONTIERS IN GENETICS. - ISSN 1664-8021. - 11:11(2020). [10.3389/fgene.2020.00346]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1392955
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