Epigenetic signatures associated with different levels of differentiation potential in human stem cells.

<h4>Background</h4>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.<h4>Methodology/prin...

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Autores principales: Pablo Aranda, Xabier Agirre, Esteban Ballestar, Enrique J Andreu, José Román-Gómez, Inés Prieto, José Ignacio Martín-Subero, Juan Cruz Cigudosa, Reiner Siebert, Manel Esteller, Felipe Prosper
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Publicado: Public Library of Science (PLoS) 2009
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spelling oai:doaj.org-article:363f57de711646819f927021eddd705e2021-11-25T06:28:09ZEpigenetic signatures associated with different levels of differentiation potential in human stem cells.1932-620310.1371/journal.pone.0007809https://doaj.org/article/363f57de711646819f927021eddd705e2009-11-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19915669/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>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.<h4>Methodology/principal findings</h4>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.<h4>Conclusions/significance</h4>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.Pablo ArandaXabier AgirreEsteban BallestarEnrique J AndreuJosé Román-GómezInés PrietoJosé Ignacio Martín-SuberoJuan Cruz CigudosaReiner SiebertManel EstellerFelipe ProsperPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 4, Iss 11, p e7809 (2009)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Pablo Aranda
Xabier Agirre
Esteban Ballestar
Enrique J Andreu
José Román-Gómez
Inés Prieto
José Ignacio Martín-Subero
Juan Cruz Cigudosa
Reiner Siebert
Manel Esteller
Felipe Prosper
Epigenetic signatures associated with different levels of differentiation potential in human stem cells.
description <h4>Background</h4>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.<h4>Methodology/principal findings</h4>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.<h4>Conclusions/significance</h4>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.
format article
author Pablo Aranda
Xabier Agirre
Esteban Ballestar
Enrique J Andreu
José Román-Gómez
Inés Prieto
José Ignacio Martín-Subero
Juan Cruz Cigudosa
Reiner Siebert
Manel Esteller
Felipe Prosper
author_facet Pablo Aranda
Xabier Agirre
Esteban Ballestar
Enrique J Andreu
José Román-Gómez
Inés Prieto
José Ignacio Martín-Subero
Juan Cruz Cigudosa
Reiner Siebert
Manel Esteller
Felipe Prosper
author_sort Pablo Aranda
title Epigenetic signatures associated with different levels of differentiation potential in human stem cells.
title_short Epigenetic signatures associated with different levels of differentiation potential in human stem cells.
title_full Epigenetic signatures associated with different levels of differentiation potential in human stem cells.
title_fullStr Epigenetic signatures associated with different levels of differentiation potential in human stem cells.
title_full_unstemmed Epigenetic signatures associated with different levels of differentiation potential in human stem cells.
title_sort epigenetic signatures associated with different levels of differentiation potential in human stem cells.
publisher Public Library of Science (PLoS)
publishDate 2009
url https://doaj.org/article/363f57de711646819f927021eddd705e
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