TFEB regulates murine liver cell fate during development and regeneration

Autor: Tuong Huynh, Alessia Calcagni, Ayrea Hurley, Milton J. Finegold, Stuart J. Forbes, Nunzia Pastore, William R. Lagor, Luca D’Orsi, Carmine Settembre, Niculin J. Herz, Marco De Giorgi, Tiemo J. Klisch, Lorenzo Brunetti, David D. Moore, Margherita Mutarelli, Andrea Ballabio, Niya Aleksieva, Annamaria Carissimo, Kangho Ho Kim
Přispěvatelé: Pastore, N., Huynh, T., Herz, N. J., Calcagni', A., Klisch, T. J., Brunetti, L., Kim, K. H., De Giorgi, M., Hurley, A., Carissimo, A., Mutarelli, M., Aleksieva, N., D'Orsi, L., Lagor, W. R., Moore, D. D., Settembre, C., Finegold, M. J., Forbes, S. J., Ballabio, A.
Jazyk: angličtina
Rok vydání: 2020
Předmět:
0301 basic medicine
Cellular differentiation
General Physics and Astronomy
Regenerative Medicine
Inbred C57BL
Oral and gastrointestinal
Transgenic
Cholangiocarcinoma
Mice
0302 clinical medicine
Stem Cell Research - Nonembryonic - Human
Models
2.1 Biological and endogenous factors
Aetiology
Promoter Regions
Genetic
Induced pluripotent stem cell
lcsh:Science
Cancer
Pediatric
Hepatocyte differentiation
Transdifferentiation
Multidisciplinary
Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
Liver Disease
Liver cell
Stem Cells
Cell Differentiation
SOX9 Transcription Factor
Cell biology
Up-Regulation
Phenotype
Liver
030220 oncology & carcinogenesis
Stem Cell Research - Nonembryonic - Non-Human
Stem cell
Protein Binding
Liver Cancer
1.1 Normal biological development and functioning
Science
Chronic Liver Disease and Cirrhosis
Down-Regulation
Mice
Transgenic
Biology
Cell fate determination
Models
Biological
Article
General Biochemistry
Genetics and Molecular Biology
Cholangiocyte
Promoter Regions
03 medical and health sciences
Rare Diseases
Genetic
Underpinning research
Spheroids
Cellular
Genetics
Animals
Regeneration
Cell Lineage
Cell Proliferation
General Chemistry
Stem Cell Research
Biological
Mice
Inbred C57BL
030104 developmental biology
Bile Duct Neoplasms
Bile Ducts
Hepatocytes
TFEB
lcsh:Q
Cellular
Spheroids
Digestive Diseases
Zdroj: Pastore, N, Huynh, T, Herz, N J, Calcagni, A, Klisch, T J, Brunetti, L, Kim, K H, De Giorgi, M, Hurley, A, Carissimo, A, Mutarelli, M, Aleksieva, N, D'Orsi, L, Lagor, W R, Moore, D D, Settembre, C, Finegold, M J, Forbes, S & Ballabio, A 2020, ' TFEB regulates murine liver cell fate during development and regeneration ', Nature Communications, vol. 11, no. 1, 2461 . https://doi.org/10.1038/s41467-020-16300-x
Nature Communications, Vol 11, Iss 1, Pp 1-14 (2020)
Nature communications, vol 11, iss 1
Nature Communications
DOI: 10.1038/s41467-020-16300-x
Popis: It is well established that pluripotent stem cells in fetal and postnatal liver (LPCs) can differentiate into both hepatocytes and cholangiocytes. However, the signaling pathways implicated in the differentiation of LPCs are still incompletely understood. Transcription Factor EB (TFEB), a master regulator of lysosomal biogenesis and autophagy, is known to be involved in osteoblast and myeloid differentiation, but its role in lineage commitment in the liver has not been investigated. Here we show that during development and upon regeneration TFEB drives the differentiation status of murine LPCs into the progenitor/cholangiocyte lineage while inhibiting hepatocyte differentiation. Genetic interaction studies show that Sox9, a marker of precursor and biliary cells, is a direct transcriptional target of TFEB and a primary mediator of its effects on liver cell fate. In summary, our findings identify an unexplored pathway that controls liver cell lineage commitment and whose dysregulation may play a role in biliary cancer.
The Transcription Factor EB (TFEB) is known to regulate cellular homeostasis and energy metabolism, but its role in cell fate determination in the liver is unknown. Here, the authors show that TFEB regulates the progenitor/cholangiocyte lineage and that its depletion prevents tissue recovery upon injury.
Databáze: OpenAIRE
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