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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 Epigenesis 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. |
Note: | Reproducció del document publicat a: http://dx.doi.org/10.1371/journal.pone.0007809 |
It is part of: | PLoS One, 2009, vol. 4, num. 11, p. e7809 |
URI: | http://hdl.handle.net/2445/69601 |
Related resource: | http://dx.doi.org/10.1371/journal.pone.0007809 |
ISSN: | 1932-6203 |
Appears in Collections: | Articles publicats en revistes (Fonaments Clínics) Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) |
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