Differential DNA Methylation Encodes Proliferation and Senescence Programs in Human Adipose-Derived Mesenchymal Stem Cells.

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 5'-azacitidine (5'-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.

journal_name

Front Genet

journal_title

Frontiers in genetics

authors

Pepin ME,Infante T,Benincasa G,Schiano C,Miceli M,Ceccarelli S,Megiorni F,Anastasiadou E,Della Valle G,Fatone G,Faenza M,Docimo L,Nicoletti GF,Marchese C,Wende AR,Napoli C

doi

10.3389/fgene.2020.00346

subject

Has Abstract

pub_date

2020-04-15 00:00:00

pages

346

issn

1664-8021

journal_volume

11

pub_type

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