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Control of liver cell fate decision by a gradient of TGFβ signaling modulated by Onecut transcription factors
Open accessAbstract
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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Citations
Cited by
Liver regeneration: biological and pathological mechanisms and implications
Michalopoulos, G. K., & Bhushan, B. (2021) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-020-0342-4 · Cited by 998
Organogenesis and development of the liver
Si-Tayeb, K., Lemaigre, F. P., & Duncan, S. A. (2010) · Developmental Cell · doi:10.1016/j.devcel.2010.01.011 · Cited by 800
Self-citationStem/progenitor cells in liver development, homeostasis, regeneration, and reprogramming
Miyajima, A., Tanaka, M., & Itoh, T. (2014) · Cell Stem Cell · doi:10.1016/j.stem.2014.04.010 · Cited by 570
Banales, J. M., Huebert, R. C., Karlsen, T., Strazzabosco, M., LaRusso, N. F., & Gores, G. J. (2019) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-019-0125-y · Cited by 517
Orchestrating liver development
Gordillo, M., Evans, T., & Gouon-Evans, V. (2015) · Development · doi:10.1242/dev.114215 · Cited by 375
Metadata
- Authors
- 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.
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2005-08-15
- Volume
- 19
- Issue
- 16
- Pages
- 1849-1854
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- OpenAlex
- W2123486220
- Cited by
- 363
- References
- 0
- Type
- posted content
- Language
- en
- Open access
- diamond
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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 & Development. https://doi.org/10.1101/gad.340305
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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