Abstract

The capacity of embryonic stem (ES) cells to differentiate to hepatocytes in culture provides a unique model system to study alcohol-induced liver injury in vitro, and ultimately to provide large amount of mature hepatocytes for transplantation in liver failure due to chronic alcoholic liver disease. Liver develops from the gut endoderm along with other major organs including the pancreas, lungs, thyroid and intestines. The experiments outlined in the proposal build on previous observations that endoderm-derived hepatoblast-like cells can be efficiently and reproducibly induced in the mouse ES cell system and seek to translate the murine ES cell differentiation program to the human ES cell program""""""""!. This application addresses questions relating to maturation of mouse ES-derived hepatoblast-like cells, to the endoderm induction in the human ES cell system and its specification to a hepatic fate and finally to mature human hepatocytes. Therefore, the ultimate goal of these studies is to develop a feasible approach to generate functional hepatocytes from mouse and human ES cells as an in vitro model to study alcohol-induced liver injury.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Exploratory Grants (P20)
Project #
5P20AA017067-05
Application #
8380260
Study Section
Special Emphasis Panel (ZAA1-BB)
Project Start
Project End
Budget Start
2012-08-01
Budget End
2013-07-31
Support Year
5
Fiscal Year
2012
Total Cost
$37,378
Indirect Cost
$15,326

  Institution

Name
Icahn School of Medicine at Mount Sinai
Department
Type
DUNS #
078861598
City
New York
State
NY
Country
United States
Zip Code
10029

  Publications

Ge, Xiaodong; Arriazu, Elena; Magdaleno, Fernando et al. (2018) High Mobility Group Box-1 Drives Fibrosis Progression Signaling via the Receptor for Advanced Glycation End Products in Mice. Hepatology 68:2380-2404
Magdaleno, Fernando; Blajszczak, Chuck C; Nieto, Natalia (2017) Key Events Participating in the Pathogenesis of  Alcoholic Liver Disease. Biomolecules 7:
Arriazu, Elena; Ge, Xiaodong; Leung, Tung-Ming et al. (2017) Signalling via the osteopontin and high mobility group box-1 axis drives the fibrogenic response to liver injury. Gut 66:1123-1137
Renault, Thibaud T; Luna-Vargas, Mark P A; Chipuk, Jerry E (2016) Mouse Liver Mitochondria Isolation, Size Fractionation, and Real-time MOMP Measurement. Bio Protoc 6:
Kocabayoglu, Peri; Zhang, David Y; Kojima, Kensuke et al. (2016) Induction and contribution of beta platelet-derived growth factor signalling by hepatic stellate cells to liver regeneration after partial hepatectomy in mice. Liver Int 36:874-82
Magdaleno, Fernando; Arriazu, Elena; Ruiz de Galarreta, Marina et al. (2016) Cartilage oligomeric matrix protein participates in the pathogenesis of liver fibrosis. J Hepatol 65:963-971
Laitman, Benjamin M; Asp, Linnéa; Mariani, John N et al. (2016) The Transcriptional Activator Krüppel-like Factor-6 Is Required for CNS Myelination. PLoS Biol 14:e1002467
Kocabayoglu, Peri; Lade, Abigale; Lee, Youngmin A et al. (2015) ?-PDGF receptor expressed by hepatic stellate cells regulates fibrosis in murine liver injury, but not carcinogenesis. J Hepatol 63:141-7
Renault, Thibaud T; Floros, Konstantinos V; Elkholi, Rana et al. (2015) Mitochondrial shape governs BAX-induced membrane permeabilization and apoptosis. Mol Cell 57:69-82
Hasegawa, Daisuke; Calvo, Veronica; Avivar-Valderas, Alvaro et al. (2015) Epithelial Xbp1 is required for cellular proliferation and differentiation during mammary gland development. Mol Cell Biol 35:1543-56

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