Control of liver cell fate decision by a gradient of TGFβ signaling modulated by Onecut transcription factors

Frédéric Clotman; Patrick Jacquemin; Nicolas Plumb-Rudewiez; Christophe E. Pierreux; Patrick Van Der Smissen; Harry C. Dietz; Pierre J. Courtoy; Guy G. Rousseau; Frédéric P. Lemaigre

doi:10.1101/gad.340305

Control of liver cell fate decision by a gradient of TGFβ signaling modulated by Onecut transcription factors

Frédéric Clotman, Patrick Jacquemin, Nicolas Plumb-Rudewiez, Christophe E. Pierreux, Patrick Van Der Smissen, Harry C. Dietz, Pierre J. Courtoy, Guy G. Rousseau, Frédéric P. Lemaigre

School of Medicine

Research output: Contribution to journal › Article

Abstract

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.

Original language	English (US)
Pages (from-to)	1849-1854
Number of pages	6
Journal	Genes and Development
Volume	19
Issue number	16
DOIs	https://doi.org/10.1101/gad.340305
State	Published - Aug 15 2005

Keywords

Activin/TGFβ signaling gradient
Hepatic differentiation
Hepatoblasts
Liver development
Onecut transcription factors

ASJC Scopus subject areas

Genetics
Developmental Biology

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10.1101/gad.340305

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Clotman, F., Jacquemin, P., Plumb-Rudewiez, N., Pierreux, C. E., Van Der Smissen, P., Dietz, H. C., Courtoy, P. J., Rousseau, G. G., & Lemaigre, F. P. (2005). Control of liver cell fate decision by a gradient of TGFβ signaling modulated by Onecut transcription factors. Genes and Development, 19(16), 1849-1854. https://doi.org/10.1101/gad.340305

Control of liver cell fate decision by a gradient of TGFβ signaling modulated by Onecut transcription factors. / Clotman, Frédéric; Jacquemin, Patrick; Plumb-Rudewiez, Nicolas; Pierreux, Christophe E.; Van Der Smissen, Patrick; Dietz, Harry C.; Courtoy, Pierre J.; Rousseau, Guy G.; Lemaigre, Frédéric P.

In: Genes and Development, Vol. 19, No. 16, 15.08.2005, p. 1849-1854.

Research output: Contribution to journal › Article

Clotman, Frédéric ; Jacquemin, Patrick ; Plumb-Rudewiez, Nicolas ; Pierreux, Christophe E. ; Van Der Smissen, Patrick ; Dietz, Harry C. ; Courtoy, Pierre J. ; Rousseau, Guy G. ; Lemaigre, Frédéric P. / Control of liver cell fate decision by a gradient of TGFβ signaling modulated by Onecut transcription factors. In: Genes and Development. 2005 ; Vol. 19, No. 16. pp. 1849-1854.

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title = "Control of liver cell fate decision by a gradient of TGFβ signaling modulated by Onecut transcription factors",

abstract = "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.",

keywords = "Activin/TGFβ signaling gradient, Hepatic differentiation, Hepatoblasts, Liver development, Onecut transcription factors",

author = "Fr{\'e}d{\'e}ric Clotman and Patrick Jacquemin and Nicolas Plumb-Rudewiez and Pierreux, {Christophe E.} and {Van Der Smissen}, Patrick and Dietz, {Harry C.} and Courtoy, {Pierre J.} and Rousseau, {Guy G.} and Lemaigre, {Fr{\'e}d{\'e}ric P.}",

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AB - 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.

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