title: DNA methylation plasticity of human adipose-derived stem cells in lineage commitment.
abstract: Adult stem cells have an enormous potential for clinical use in regenerative medicine that avoids many of the drawbacks characteristic of embryonic stem cells and induced pluripotent stem cells. In this context, easily obtainable human adipose-derived stem cells offer an interesting option for future strategies in regenerative medicine. However, little is known about their repertoire of differentiation capacities, how closely they resemble the target primary tissues, and the potential safety issues associated with their use. DNA methylation is one of the most widely recognized epigenetic factors involved in cellular identity, prompting us to consider how the analyses of 27,578 CpG sites in the genome of these cells under different conditions reflect their different natural history. We show that human adipose-derived stem cells generate myogenic and osteogenic lineages that share much of the DNA methylation landscape characteristic of primary myocytes and osteocytes. Most important, adult stem cells and in vitro-generated myocytes and osteocytes display a significantly different DNA methylome from that observed in transformed cells from these tissue types, such as rhabdomyosarcoma and osteosarcoma. These results suggest that the plasticity of the DNA methylation patterns plays an important role in lineage commitment of adult stem cells and that it could be used for clinical purposes as a biomarker of efficient and safely differentiated cells.
authors.affiliation: Cancer Epigenetics Group, Cancer Epigenetics and Biology Program, Bellvitge Biomedical Biomedical Research Institute, Barcelona, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Berdasco
authors.forename: Consolación
authors.initials: C
authors.lastname: Melguizo
authors.forename: Jose
authors.initials: J
authors.lastname: Prados
authors.forename: Antonio
authors.initials: A
authors.lastname: Gómez
authors.forename: Miguel
authors.initials: M
authors.lastname: Alaminos
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Pujana
authors.forename: Miguel
authors.initials: M
authors.lastname: Lopez
authors.forename: Fernando
authors.initials: F
authors.lastname: Setien
authors.forename: Raul
authors.initials: R
authors.lastname: Ortiz
authors.forename: Inma
authors.initials: I
authors.lastname: Zafra
authors.forename: Antonia
authors.initials: A
authors.lastname: Aranega
authors.forename: Manel
authors.initials: M
authors.lastname: Esteller
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D000328:Adult; D002454:Cell Differentiation / Q000235:genetics; D045744:Cell Line, Tumor; D019070:Cell Lineage / Q000235:genetics*; D002478:Cells, Cultured; D019175:DNA Methylation / Q000235:genetics*; D044127:Epigenesis, Genetic; D006801:Humans; D008875:Middle Aged; D039902:Multipotent Stem Cells / Q000166:cytology / Q000378:metabolism; D032342:Muscle Cells / Q000166:cytology / Q000378:metabolism; D024510:Muscle Development / Q000235:genetics; D010011:Osteocytes / Q000166:cytology / Q000378:metabolism; D010012:Osteogenesis / Q000235:genetics; D010641:Phenotype; D011401:Promoter Regions, Genetic / Q000235:genetics; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism*