Locking the Fate: How PROX1 Represses Plasticity and Liver Cancer

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"...

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Bibliographic Details
Published inCellular reprogramming Vol. 27; no. 3; p. 102
Main Authors Lee, Seung-Won, Kim, Jungsun
Format Journal Article
LanguageEnglish
Published United States 01.05.2025
Subjects
Animals
Cell Differentiation
Cell Lineage
Cell Plasticity
Cholangiocarcinoma - metabolism
Cholangiocarcinoma - pathology
Hepatocytes - metabolism
Homeodomain Proteins - genetics
Homeodomain Proteins - metabolism
Humans
Liver Neoplasms - genetics
Liver Neoplasms - metabolism
Liver Neoplasms - pathology
Prospero-Related Homeobox 1 Protein
Tumor Suppressor Proteins - genetics
Tumor Suppressor Proteins - metabolism
plasticity
prospero homeobox protein 1 (PROX1)
hepatocytic safeguard repressor cell identity
Online AccessGet more information
ISSN2152-4998
DOI10.1089/cell.2025.0013

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Summary: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.
ISSN:2152-4998
DOI:10.1089/cell.2025.0013