Lentiviral transduction of CD34(+) cells induces genome-wide epigenetic modifications.

Epigenetic modifications may occur during in vitro manipulations of stem cells but these effects have remained unexplored in the context of cell and gene therapy protocols. In an experimental model of ex vivo gene modification for hematopoietic gene therapy, human CD34(+) cells were cultured shortly...

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Autores principales:	Yoshiaki Yamagata, Véronique Parietti, Daniel Stockholm, Guillaume Corre, Catherine Poinsignon, Nizar Touleimat, Damien Delafoy, Céline Besse, Jörg Tost, Anne Galy, András Paldi
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/54789a2199b841f1a79a27d8bed82145
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spelling	oai:doaj.org-article:54789a2199b841f1a79a27d8bed821452021-11-18T08:09:36ZLentiviral transduction of CD34(+) cells induces genome-wide epigenetic modifications.1932-620310.1371/journal.pone.0048943https://doaj.org/article/54789a2199b841f1a79a27d8bed821452012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23145033/?tool=EBIhttps://doaj.org/toc/1932-6203Epigenetic modifications may occur during in vitro manipulations of stem cells but these effects have remained unexplored in the context of cell and gene therapy protocols. In an experimental model of ex vivo gene modification for hematopoietic gene therapy, human CD34(+) cells were cultured shortly in the presence of cytokines then with a gene transfer lentiviral vector (LV) expected to transduce cells but to have otherwise limited biological effects on the cells. At the end of the culture, the population of cells remained largely similar at the phenotypic level but some epigenetic changes were evident. Exposure of CD34(+) cells to cytokines increased nuclear expression of epigenetic regulators SIRT1 or DNMT1 and caused genome-wide DNA methylation changes. Surprisingly, the LV caused additional and distinct effects. Large-scale genomic DNA methylation analysis showed that balanced methylation changes occurred in about 200 genes following culture of CD34(+) cells in the presence of cytokines but 900 genes were modified following addition of the LV, predominantly increasing CpG methylation. Epigenetic effects resulting from ex vivo culture and from the use of LV may constitute previously unsuspected sources of biological effects in stem cells and may provide new biomarkers to rationally optimize gene and cell therapy protocols.Yoshiaki YamagataVéronique PariettiDaniel StockholmGuillaume CorreCatherine PoinsignonNizar TouleimatDamien DelafoyCéline BesseJörg TostAnne GalyAndrás PaldiPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 11, p e48943 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yoshiaki Yamagata Véronique Parietti Daniel Stockholm Guillaume Corre Catherine Poinsignon Nizar Touleimat Damien Delafoy Céline Besse Jörg Tost Anne Galy András Paldi Lentiviral transduction of CD34(+) cells induces genome-wide epigenetic modifications.
description	Epigenetic modifications may occur during in vitro manipulations of stem cells but these effects have remained unexplored in the context of cell and gene therapy protocols. In an experimental model of ex vivo gene modification for hematopoietic gene therapy, human CD34(+) cells were cultured shortly in the presence of cytokines then with a gene transfer lentiviral vector (LV) expected to transduce cells but to have otherwise limited biological effects on the cells. At the end of the culture, the population of cells remained largely similar at the phenotypic level but some epigenetic changes were evident. Exposure of CD34(+) cells to cytokines increased nuclear expression of epigenetic regulators SIRT1 or DNMT1 and caused genome-wide DNA methylation changes. Surprisingly, the LV caused additional and distinct effects. Large-scale genomic DNA methylation analysis showed that balanced methylation changes occurred in about 200 genes following culture of CD34(+) cells in the presence of cytokines but 900 genes were modified following addition of the LV, predominantly increasing CpG methylation. Epigenetic effects resulting from ex vivo culture and from the use of LV may constitute previously unsuspected sources of biological effects in stem cells and may provide new biomarkers to rationally optimize gene and cell therapy protocols.
format	article
author	Yoshiaki Yamagata Véronique Parietti Daniel Stockholm Guillaume Corre Catherine Poinsignon Nizar Touleimat Damien Delafoy Céline Besse Jörg Tost Anne Galy András Paldi
author_facet	Yoshiaki Yamagata Véronique Parietti Daniel Stockholm Guillaume Corre Catherine Poinsignon Nizar Touleimat Damien Delafoy Céline Besse Jörg Tost Anne Galy András Paldi
author_sort	Yoshiaki Yamagata
title	Lentiviral transduction of CD34(+) cells induces genome-wide epigenetic modifications.
title_short	Lentiviral transduction of CD34(+) cells induces genome-wide epigenetic modifications.
title_full	Lentiviral transduction of CD34(+) cells induces genome-wide epigenetic modifications.
title_fullStr	Lentiviral transduction of CD34(+) cells induces genome-wide epigenetic modifications.
title_full_unstemmed	Lentiviral transduction of CD34(+) cells induces genome-wide epigenetic modifications.
title_sort	lentiviral transduction of cd34(+) cells induces genome-wide epigenetic modifications.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/54789a2199b841f1a79a27d8bed82145
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Lentiviral transduction of CD34(+) cells induces genome-wide epigenetic modifications.

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