Signaling networks in human pluripotent stem cells

Maintaining a finely-balanced network of signaling inputs is critical for the maintenance of pluripotent stem cells. Together, signaling pathways achieve this by maintaining a long-term, proliferative state while suppressing differentiation. Although the major pathways involved in pluripotency have been known for some time, it was not previously clear how they function in concert to maintain stem cell identity. Recent work has identified a signaling network involving cross-talk between PI3K, TGFβ, MAPK and Wnt pathways that culminate in a finely-balanced molecular switch that determines the fate of pluripotent cells.

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► Signaling in pluripotent stem cells is a complex, dynamic process.
► Multiple signaling pathways are required for maintenance of the stem cell state: Fgf/MAPK, TGFβ/SMAD2,3 and insulin/PI3K.
► These pathways are highly interactive and form a finely-balanced signaling network.
► Thresholds, temporal changes and combinatorial effects make important contributions to cell fate outcomes.