title: Epigenetic signatures associated with different levels of differentiation potential in human stem cells.
abstract: BACKGROUND
  The therapeutic use of multipotent stem cells depends on their differentiation potential, which has been shown to be variable for different populations. These differences are likely to be the result of key changes in their epigenetic profiles.
  
  
  RESULTS
  to address this issue, we have investigated the levels of epigenetic regulation in well characterized populations of pluripotent embryonic stem cells (ESC) and multipotent adult stem cells (ASC) at the trancriptome, methylome, histone modification and microRNA levels. Differences in gene expression profiles allowed classification of stem cells into three separate populations including ESC, multipotent adult progenitor cells (MAPC) and mesenchymal stromal cells (MSC). The analysis of the PcG repressive marks, histone modifications and gene promoter methylation of differentiation and pluripotency genes demonstrated that stem cell populations with a wider differentiation potential (ESC and MAPC) showed stronger representation of epigenetic repressive marks in differentiation genes and that this epigenetic signature was progressively lost with restriction of stem cell potential. Our analysis of microRNA established specific microRNA signatures suggesting specific microRNAs involved in regulation of pluripotent and differentiation genes.
  
  
  CONCLUSIONS
  Our study leads us to propose a model where the level of epigenetic regulation, as a combination of DNA methylation and histone modification marks, at differentiation genes defines degrees of differentiation potential from progenitor and multipotent stem cells to pluripotent stem cells.
authors.affiliation: Hematology Department and Area of Cell Therapy, Clínica Universidad de Navarra, Foundation for Applied Medical Research, University of Navarra, Pamplona, Spain.
authors.forename: Pablo
authors.initials: P
authors.lastname: Aranda
authors.forename: Xabier
authors.initials: X
authors.lastname: Agirre
authors.forename: Esteban
authors.initials: E
authors.lastname: Ballestar
authors.forename: Enrique J
authors.initials: EJ
authors.lastname: Andreu
authors.forename: José
authors.initials: J
authors.lastname: Román-Gómez
authors.forename: Inés
authors.initials: I
authors.lastname: Prieto
authors.forename: José Ignacio
authors.initials: JI
authors.lastname: Martín-Subero
authors.forename: Juan Cruz
authors.initials: JC
authors.lastname: Cigudosa
authors.forename: Reiner
authors.initials: R
authors.lastname: Siebert
authors.forename: Manel
authors.initials: M
authors.lastname: Esteller
authors.forename: Felipe
authors.initials: F
authors.lastname: Prosper
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D000328:Adult; D002454:Cell Differentiation; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D020869:Gene Expression Profiling; D006657:Histones / Q000378:metabolism; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology; D035683:MicroRNAs / Q000378:metabolism; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D011401:Promoter Regions, Genetic; D013234:Stem Cells / Q000166:cytology*; D014158:Transcription, Genetic
chemical_list: D006657:Histones; D035683:MicroRNAs