2016年11月
The mevalonate pathway regulates primitive streak formation via protein farnesylation
SCIENTIFIC REPORTS
- 巻
- 6
- 号
- 開始ページ
- 37697
- 終了ページ
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1038/srep37697
- 出版者・発行元
- NATURE PUBLISHING GROUP
The primitive streak in peri-implantation embryos forms the mesoderm and endoderm and controls cell differentiation. The metabolic cues regulating primitive streak formation remain largely unknown. Here we utilised a mouse embryonic stem (ES) cell differentiation system and a library of well-characterised drugs to identify these metabolic factors. We found that statins, which inhibit the mevalonate metabolic pathway, suppressed primitive streak formation in vitro and in vivo. Using metabolomics and pharmacologic approaches we identified the downstream signalling pathway of mevalonate and revealed that primitive streak formation requires protein farnesylation but not cholesterol synthesis. A tagging-via-substrate approach revealed that nuclear lamin B1 and small G proteins were farnesylated in embryoid bodies and important for primitive streak gene expression. In conclusion, protein farnesylation driven by the mevalonate pathway is a metabolic cue essential for primitive streak formation.
- リンク情報
- ID情報
-
- DOI : 10.1038/srep37697
- ISSN : 2045-2322
- Web of Science ID : WOS:000392064000001