Control of liver cell fate decision by a gradient of TGFβ signaling modulated by Onecut transcription factors
Copyright policy )Control of liver cell fate decision by a gradient of TGFβ signaling modulated by Onecut transcription factors
During liver development, hepatocytes and biliary cells differentiate from common progenitors called hepatoblasts. The factors that control hepatoblast fate decision are unknown. Here we report that a gradient of activin/TGFβ signaling controls hepatoblast differentiation. High activin/TGFβ signaling is required near the portal vein for differentiation of biliary cells. The Onecut transcription factors HNF-6 and OC-2 inhibit activin/TGFβ signaling in the parenchyma, and this allows normal hepatocyte differentiation. In the absence of Onecut factors, the shape of the activin/TGFβ gradient is perturbed and the hepatoblasts differentiate into hybrid cells that display characteristics of both hepatocytes and biliary cells. Thus, a gradient of activin/TGFβ signaling modulated by Onecut factors is required to segregate the hepatocytic and the biliary lineages.
- Université Catholique de Louvain Belgium
- Johns Hopkins Medicine United States
- John Hopkins University School of Medecine United States
- Johns Hopkins University School of Medicine United States
- Johns Hopkins University Sch of Medicine United States
Homeodomain Proteins, Mice, Knockout, Liver development, Hepatoblasts, Hepatic differentiation, Cell Differentiation, Mice, Transgenic, Activins, Onecut transcription factors, Hepatocyte Nuclear Factor 6, Mice, Fetus, Transforming Growth Factor beta, Hepatocytes, Trans-Activators, Animals, Activin/TGFbeta signaling gradient, Signal Transduction, Transcription Factors
Homeodomain Proteins, Mice, Knockout, Liver development, Hepatoblasts, Hepatic differentiation, Cell Differentiation, Mice, Transgenic, Activins, Onecut transcription factors, Hepatocyte Nuclear Factor 6, Mice, Fetus, Transforming Growth Factor beta, Hepatocytes, Trans-Activators, Animals, Activin/TGFbeta signaling gradient, Signal Transduction, Transcription Factors
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