期刊
CELL STEM CELL
卷 8, 期 1, 页码 46-58出版社
CELL PRESS
DOI: 10.1016/j.stem.2010.11.027
关键词
-
资金
- National Natural Science Foundation [91019929, 30911130361, 31000625]
- National High Technology Research and Development Program of China [2009CB941100, 2007CB947904, 2007CB948004, 2101CB945200, 2007CB947101]
- Shanghai Science & Technology Developmental Foundations [08dj1400502, 07DZ22919]
- Shanghai Leading Academic Discipline Project [S30201]
Self-renewal and pluripotency are hallmarks of embryonic stem cells (ESCs). However, the signaling pathways that trigger their transition from self-renewal to differentiation remain elusive. Here, we report that calcineurin-NFAT signaling is both necessary and sufficient to switch ESCs from an undifferentiated state to lineage-specific cells and that the inhibition of this pathway can maintain long-term ESC self-renewal independent of leukemia inhibitory factor. Mechanistically, this pathway converges with the Erk1/2 pathway to regulate Src expression and promote the epithelial-mesenchymal transition (EMT), a process required for lineage specification in response to differentiation stimuli. Furthermore, calcineurin-NFAT signaling is activated when the earliest differentiation event occurs in mouse embryos, and its inhibition disrupts extraembryonic lineage development. Collectively, our results demonstrate that the NFAT and Erk1/2 cascades form a signaling switch for early lineage segregation in mouse ESCs and provide significant insights into the regulation of the balance between ESC self-renewal and early lineage specification,
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据