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Maintaining Pluripotency

Autoinductive FGF4/Erk signaling poises embryonic stem (ES) cells for lineage entry and must be resisted to allow self-renewal.

(A) Oct4 and Sox2 direct expression of fgf4 and poise ES cells for lineage commitment. Elevated Erk activity provides a signal that renders pluripotent cells susceptible to lineage inductive cues.

(B) Self-renewal of the pluripotent ES cell state requires overcoming the FGF4/Erk signal. The actions of FGF can be (1) blocked by selective pharmacological inhibitors of the FGF receptor (FGFR) and of Mek; (2) reversed by constitutive expression of Nanog; (3) counteracted by blockade of commitment effectors by the cytokine leukemia inhibitory factor (LIF) and the morphogen BMP4.

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