西亚试剂：Calcineurin-NFAT Signaling Critically Regulates Early Linea

Calcineurin-NFAT Signaling Critically Regulates Early Lineage Specification in Mouse Embryonic Stem Cells and Embryos

Li X, Zhu L, Yang A, Lin J, Tang F, Jin S, Wei Z, Li J and Jin Y*.

Highlights

Calcineurin-NFAT signaling triggers lineage commitment in embryonic stem cells

Src is a key player downstream of the NFAT and Erk1/2 pathways

Src-mediated signaling promotes epithelial to mesenchymal transition

Calcineurin-NFAT signaling is required for early embryonic lineage development

Summary

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.

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