TFEB regulates murine liver cell fate during development and regeneration.

Animals Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / metabolism Bile Duct Neoplasms / pathology Bile Ducts / metabolism Cell Differentiation Cell Lineage Cell Proliferation Cholangiocarcinoma / pathology Down-Regulation / genetics Hepatocytes / cytology Liver / cytology Mice, Inbred C57BL Mice, Transgenic Models, Biological Phenotype Promoter Regions, Genetic / genetics Protein Binding Regeneration / physiology SOX9 Transcription Factor / genetics Spheroids, Cellular / cytology Stem Cells / cytology Up-Regulation / genetics

Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
18 05 2020
Historique:
received: 08 01 2020
accepted: 20 04 2020
entrez: 20 5 2020
pubmed: 20 5 2020
medline: 13 8 2020
Statut: epublish

Résumé

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.

Identifiants

DOI: 10.1038/s41467-020-16300-x PMID: 32424153 PMC: PMC7235048
pubmed: 32424153
doi: 10.1038/s41467-020-16300-x
pii: 10.1038/s41467-020-16300-x
pmc: PMC7235048
doi:

Substances chimiques

Basic Helix-Loop-Helix Leucine Zipper Transcription Factors 0
SOX9 Transcription Factor 0
Tcfeb protein, mouse 0

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

2461

Subventions

Organisme : NINDS NIH HHS
ID : R01 NS078072
Pays : United States
Organisme : NIH HHS
ID : S10 OD016167
Pays : United States
Organisme : Medical Research Council
ID : MR/K017047/1
Pays : United Kingdom
Organisme : NICHD NIH HHS
ID : U54 HD083092
Pays : United States
Organisme : NICHD NIH HHS
ID : P50 HD103555
Pays : United States
Organisme : Medical Research Council
ID : MR/R015635/1
Pays : United Kingdom

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Auteurs

Nunzia Pastore (N)

Jan and Dan Duncan Neurological Research Institute, Texas Children Hospital, Houston, TX, 77030, USA. pastore@tigem.it.
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, 77030, USA. pastore@tigem.it.
ORCID: 0000-0002-8701-5592

Tuong Huynh (T)

Jan and Dan Duncan Neurological Research Institute, Texas Children Hospital, Houston, TX, 77030, USA.
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, 77030, USA.

Niculin J Herz (NJ)

Jan and Dan Duncan Neurological Research Institute, Texas Children Hospital, Houston, TX, 77030, USA.
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, 77030, USA.

Alessia Calcagni' (A)

Jan and Dan Duncan Neurological Research Institute, Texas Children Hospital, Houston, TX, 77030, USA.
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, 77030, USA.
ORCID: 0000-0002-1946-5815

Tiemo J Klisch (TJ)

Jan and Dan Duncan Neurological Research Institute, Texas Children Hospital, Houston, TX, 77030, USA.
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, 77030, USA.

Lorenzo Brunetti (L)

Stem Cells and Regenerative Medicine Center, Baylor College of Medicine, Houston, TX, 77030, USA.
Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX, 77030, USA.
ORCID: 0000-0003-2624-8576

Kangho Ho Kim (KH)

Department of Molecular and Cell Biology, Baylor College of Medicine, Houston, TX, 77030, USA.

Marco De Giorgi (M)

Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX, 77030, USA.

Ayrea Hurley (A)

Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX, 77030, USA.

Annamaria Carissimo (A)

Telethon Institute of Genetics and Medicine (TIGEM), Pozzuoli, NA, 80078, Italy.

Margherita Mutarelli (M)

Telethon Institute of Genetics and Medicine (TIGEM), Pozzuoli, NA, 80078, Italy.

Niya Aleksieva (N)

MRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh, EH16 4UU, UK.
ORCID: 0000-0002-7887-5494

Luca D'Orsi (L)

Telethon Institute of Genetics and Medicine (TIGEM), Pozzuoli, NA, 80078, Italy.

William R Lagor (WR)

Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX, 77030, USA.

David D Moore (DD)

Department of Molecular and Cell Biology, Baylor College of Medicine, Houston, TX, 77030, USA.
ORCID: 0000-0002-5151-9748

Carmine Settembre (C)

Telethon Institute of Genetics and Medicine (TIGEM), Pozzuoli, NA, 80078, Italy.
Department of Translational Medicine, Medical Genetics, Federico II University, Naples, 80131, Italy.

Milton J Finegold (MJ)

Department of Pathology, Baylor College of Medicine, Houston, TX, 77030, USA.

Stuart J Forbes (SJ)

MRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh, EH16 4UU, UK.

Andrea Ballabio (A)

Jan and Dan Duncan Neurological Research Institute, Texas Children Hospital, Houston, TX, 77030, USA. ballabio@tigem.it.
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, 77030, USA. ballabio@tigem.it.
Telethon Institute of Genetics and Medicine (TIGEM), Pozzuoli, NA, 80078, Italy. ballabio@tigem.it.
Department of Translational Medicine, Medical Genetics, Federico II University, Naples, 80131, Italy. ballabio@tigem.it.
ORCID: 0000-0003-1381-4604

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › TFEB regulates murine liver cell fate during...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Facteurs de transcription › Facteurs de transcription à motif basique et à glissière à leucines › Facteurs de transcription à motifs basiques hélice-boucle-hélice et à glissière à leucines › TFEB regulates murine liver cell fate during...
questionsmedicales.fr › Maladies de l'appareil digestif › Tumeurs de l'appareil digestif › Tumeurs des voies biliaires › Tumeurs des canaux biliaires › TFEB regulates murine liver cell fate during...
questionsmedicales.fr › Système digestif › Voies biliaires › Conduits biliaires › TFEB regulates murine liver cell fate during...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Différenciation cellulaire › TFEB regulates murine liver cell fate during...
questionsmedicales.fr › Phénomènes physiologiques des appareils urinaire et reproducteur › Phénomènes physiologiques de la reproduction › Reproduction › Développement embryonnaire et foetal › Développement embryonnaire › Lignage cellulaire › TFEB regulates murine liver cell fate during...
questionsmedicales.fr › Phénomènes physiologiques › Croissance et développement › Croissance › Processus de croissance cellulaire › Prolifération cellulaire › TFEB regulates murine liver cell fate during...
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