title: The class I-specific HDAC inhibitor MS-275 modulates the differentiation potential of mouse embryonic stem cells.
abstract: Exploitation of embryonic stem cells (ESC) for therapeutic use and biomedical applications is severely hampered by the risk of teratocarcinoma formation. Here, we performed a screen of selected epi-modulating compounds and demonstrate that a transient exposure of mouse ESC to MS-275 (Entinostat), a class I histone deacetylase inhibitor (HDAC), modulates differentiation and prevents teratocarcinoma formation. Morphological and molecular data indicate that MS-275-primed ESCs are committed towards neural differentiation, which is supported by transcriptome analyses. Interestingly, in vitro withdrawal of MS-275 reverses the primed cells to the pluripotent state. In vivo, MS275-primed ES cells injected into recipient mice give only rise to benign teratomas but not teratocarcinomas with prevalence of neural-derived structures. In agreement, MS-275-primed ESC are unable to colonize blastocysts. These findings provide evidence that a transient alteration of acetylation alters the ESC fate.
authors.affiliation: Dipartimento di Biochimica, Biofisica e Patologia Generale, Seconda Università degli Studi di Napoli , Vico L. De Crecchio 7, 80138 Napoli , Italy ; Department of Molecular Biology, Faculties of Science and Medicine, Radboud University, Nijmegen Center for Molecular Life Sciences , 6500 HB Nijmegen , The Netherlands.
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Franci
authors.forename: Laura
authors.initials: L
authors.lastname: Casalino
authors.forename: Francesca
authors.initials: F
authors.lastname: Petraglia
authors.forename: Marco
authors.initials: M
authors.lastname: Miceli
authors.forename: Roberta
authors.initials: R
authors.lastname: Menafra
authors.forename: Branka
authors.initials: B
authors.lastname: Radic
authors.forename: Valeria
authors.initials: V
authors.lastname: Tarallo
authors.forename: Monica
authors.initials: M
authors.lastname: Vitale
authors.forename: Marzia
authors.initials: M
authors.lastname: Scarfò
authors.forename: Gabriella
authors.initials: G
authors.lastname: Pocsfalvi
authors.forename: Alfonso
authors.initials: A
authors.lastname: Baldi
authors.forename: Concetta
authors.initials: C
authors.lastname: Ambrosino
authors.forename: Nicola
authors.initials: N
authors.lastname: Zambrano
authors.forename: Eduardo
authors.initials: E
authors.lastname: Patriarca
authors.forename: Sandro
authors.initials: S
authors.lastname: De Falco
authors.forename: Gabriella
authors.initials: G
authors.lastname: Minchiotti
authors.forename: Hendrik G
authors.initials: HG
authors.lastname: Stunnenberg
authors.forename: Lucia
authors.initials: L
authors.lastname: Altucci
keywords: Epigenetic; HDACi; Stem cell