{"doi":"10.3389/fgene.2020.00346","title":"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":"Frontiers in Genetics","year":2020,"id":76769,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":20,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9517,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":400052,"name":"Teresa Infante","orcid":"0000-0002-1764-9610","position":1,"is_corresponding":false},{"id":242684,"name":"Giuditta Benincasa","orcid":"0000-0002-7552-3522","position":2,"is_corresponding":false},{"id":400053,"name":"Concetta Schiano","orcid":"0000-0002-2570-6910","position":3,"is_corresponding":false},{"id":400054,"name":"Marco Miceli","orcid":"0000-0001-5806-1488","position":4,"is_corresponding":false},{"id":400055,"name":"Simona Ceccarelli","orcid":"0000-0001-8789-7719","position":5,"is_corresponding":false},{"id":400056,"name":"Francesca Megiorni","orcid":"0000-0003-3705-3248","position":6,"is_corresponding":false},{"id":242680,"name":"Eleni Anastasiadou","orcid":"0000-0003-0212-6734","position":7,"is_corresponding":false},{"id":400057,"name":"Giovanni Della Valle","orcid":"0000-0002-5424-6335","position":8,"is_corresponding":false},{"id":400058,"name":"Gerardo Fatone","orcid":"0000-0003-2578-7420","position":9,"is_corresponding":false},{"id":400059,"name":"Mario Faenza","orcid":"0000-0002-0077-8977","position":10,"is_corresponding":false},{"id":400060,"name":"Ludovico Docimo","orcid":"0000-0001-5587-9452","position":11,"is_corresponding":false},{"id":400061,"name":"Giovanni Francesco Nicoletti","orcid":"0000-0003-4586-0314","position":12,"is_corresponding":false},{"id":242690,"name":"Cinzia Marchese","orcid":"0000-0002-9280-8917","position":13,"is_corresponding":false},{"id":232325,"name":"Adam R. Wende","orcid":"0000-0002-5536-4675","position":14,"is_corresponding":false},{"id":242691,"name":"Claudio Napoli","orcid":"0000-0002-5455-555X","position":15,"is_corresponding":false},{"id":305270,"name":"Mark E. Pepin","orcid":"0000-0003-0114-560X","position":0,"is_corresponding":true}],"reference_count":31,"raw_metadata":null,"created_at":"2026-07-18T21:48:27.511277Z","pmid":"32351540","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}