A Transcriptional Ridge in the Waddington Landscape. The Waddington landscape model, proposed in 1957, provides a powerful framework for understanding cell fate determination (Waddington, 1957). As development progresses, cells become restricted to distinct fates, separated by high “ridges” that prevent identity switching. A recent study in Nature Genetics uncovers such a ridge in hepatocyte lineage specification (Lim et al., 2025). Lim et al. report that prospero homeobox protein 1 (PROX1) acts as a hepatocyte-specific safeguard repressor, ensuring lineage stability by actively suppressing alternative cell fates and preventing cholangiocarcinoma development.
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