TY - JOUR
T1 - The class I-specific HDAC inhibitor MS-275 modulates the differentiation potential of mouse embryonic stem cells
AU - Franci, Gianluigi
AU - Casalino, Laura
AU - Petraglia, Francesca
AU - Miceli, Marco
AU - Menafra, Roberta
AU - Radic, Branka
AU - Tarallo, Valeria
AU - Vitale, Monica
AU - Scarfò, Marzia
AU - Pocsfalvi, Gabriella
AU - Baldi, Alfonso
AU - Ambrosino, Concetta
AU - Zambrano, Nicola
AU - Patriarca, Eduardo
AU - De Falco, Sandro
AU - Minchiotti, Gabriella
AU - Stunnenberg, Hendrik G.
AU - Altucci, Lucia
N1 - Publisher Copyright:
© 2013 Published by The Company of Biologists Ltd.
PY - 2013/10/15
Y1 - 2013/10/15
N2 - 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.
AB - 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.
KW - Epigenetic
KW - HDACi
KW - Stem cell
UR - http://www.scopus.com/inward/record.url?scp=84979581717&partnerID=8YFLogxK
U2 - 10.1242/bio.20135587
DO - 10.1242/bio.20135587
M3 - Article
AN - SCOPUS:84979581717
SN - 2046-6390
VL - 2
SP - 1070
EP - 1077
JO - Biology Open
JF - Biology Open
IS - 10
ER -