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Title: Epigenetic signatures associated with different levels of differentiation potential in human stem cells
Author: Aranda, Pablo
Agirre, Xabier
Ballestar Tarín, Esteban
Andreu, Enrique J.
Román-Gómez, José
Prieto, Inés
Martín-Subero, José Ignacio
Cruz Cigudosa, Juan
Siebert, Reiner
Esteller, Manel
Prosper, Felipe
Keywords: Epigènesi
Cèl·lules mare
Diferenciació cel·lular
Transcripció genètica
Stem cells
Cell diferentiation
Genetic transcription
Issue Date: 2009
Publisher: Public Library of Science (PLoS)
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. METHODOLOGY/PRINCIPAL FINDINGS: 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/SIGNIFICANCE: 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.
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It is part of: PLoS One, 2009, vol. 4, num. 11, p. e7809
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ISSN: 1932-6203
Appears in Collections:Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
Articles publicats en revistes (Fonaments Clínics)

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