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Altucci, L.

Ambrosino, C.

Baldi, A.

Casalino, L.

Falco, S. De

Franci, G.

Menafra, R.

Miceli, M.

Minchiotti, G.

Patriarca, E.

Petraglia, F.

Pocsfalvi, G.

Radic, B.

Scarfo, M.

Stunnenberg, H.G.

Tarallo, V.

Vitale, M.

Zambrano, N.

Biology Open

PubMed

Radboud Repository

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

: 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

Franci, Gianluigi

Casalino, Laura

Petraglia, Francesca

Miceli, Marco

Menafra, Roberta

Radic, Branka

Tarallo, Valeria

Vitale, Monica

Scarfò, Marzia

Pocsfalvi, Gabriella

Baldi, Alfonso

Ambrosino, Concetta

Zambrano, Nicola

Patriarca, Eduardo

De Falco, Sandro

Minchiotti, Gabriella

Stunnenberg, Hendrik G

Altucci, Lucia

Archivio della Ricerca - Università di Salerno

NARCIS 

Summary
               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.</jats:p

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

Crossref

Summary
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

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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

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

Abstract

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Radboud Repository

Archivio della Ricerca - Università di Salerno

NARCIS

Crossref

Directory of Open Access Journals

Archivio della ricerca - Università degli studi di Napoli Federico II