The class I-specific HDAC inhibitor MS-275 modulates the differentiation potential of mouse embryonic stem cells

Gianluigi Franci, Laura Casalino, Francesca Petraglia, Marco Miceli, Roberta Menafra, Branka Radic, Valeria Tarallo, Monica Vitale, Marzia Scarfò, Gabriella Pocsfalvi, Alfonso Baldi, Concetta Ambrosino, Nicola Zambrano, Eduardo Patriarca, Sandro De Falco, Gabriella Minchiotti, Hendrik G. Stunnenberg, Lucia Altucci

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

17 Citaten (Scopus)

Samenvatting

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.

Originele taal-2Engels
Pagina's (van-tot)1070-1077
Aantal pagina's8
TijdschriftBiology Open
Volume2
Nummer van het tijdschrift10
DOI's
StatusGepubliceerd - 15 okt. 2013
Extern gepubliceerdJa

Vingerafdruk

Duik in de onderzoeksthema's van 'The class I-specific HDAC inhibitor MS-275 modulates the differentiation potential of mouse embryonic stem cells'. Samen vormen ze een unieke vingerafdruk.

Citeer dit