期刊
BIOLOGY OPEN
卷 2, 期 10, 页码 1070-1077出版社
COMPANY BIOLOGISTS LTD
DOI: 10.1242/bio.20135587
关键词
Stem cell; Epigenetic; HDACi
类别
资金
- Epigenomics Flagship Project 'EPIGEN' (MIUR-CNR)
- EU
- Blueprint [282510]
- ATLAS [221952]
- Italian Association for Cancer Research [AIRC grant] [11812, 11599]
- Italian Ministry of University and Research [PRIN_2009PX2T2E_004, PON002782, PON01_01227]
- Medical Research in Italy [RBNE08HM7T-003]
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, MS275-primed ESC are unable to colonize blastocysts. These findings provide evidence that a transient alteration of acetylation alters the ESC fate. (C) 2013. Published by The Company of Biologists Ltd.
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