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TFEB regulates murine liver cell fate during development and regeneration

Author

Listed:
  • Nunzia Pastore

    (Texas Children Hospital
    Baylor College of Medicine)

  • Tuong Huynh

    (Texas Children Hospital
    Baylor College of Medicine)

  • Niculin J. Herz

    (Texas Children Hospital
    Baylor College of Medicine)

  • Alessia Calcagni’

    (Texas Children Hospital
    Baylor College of Medicine)

  • Tiemo J. Klisch

    (Texas Children Hospital
    Baylor College of Medicine)

  • Lorenzo Brunetti

    (Baylor College of Medicine
    Baylor College of Medicine)

  • Kangho Ho Kim

    (Baylor College of Medicine)

  • Marco De Giorgi

    (Baylor College of Medicine)

  • Ayrea Hurley

    (Baylor College of Medicine)

  • Annamaria Carissimo

    (Telethon Institute of Genetics and Medicine (TIGEM))

  • Margherita Mutarelli

    (Telethon Institute of Genetics and Medicine (TIGEM))

  • Niya Aleksieva

    (University of Edinburgh)

  • Luca D’Orsi

    (Telethon Institute of Genetics and Medicine (TIGEM))

  • William R. Lagor

    (Baylor College of Medicine)

  • David D. Moore

    (Baylor College of Medicine)

  • Carmine Settembre

    (Telethon Institute of Genetics and Medicine (TIGEM)
    Federico II University)

  • Milton J. Finegold

    (Baylor College of Medicine)

  • Stuart J. Forbes

    (University of Edinburgh)

  • Andrea Ballabio

    (Texas Children Hospital
    Baylor College of Medicine
    Telethon Institute of Genetics and Medicine (TIGEM)
    Federico II University)

Abstract

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.

Suggested Citation

  • Nunzia Pastore & Tuong Huynh & Niculin J. Herz & Alessia Calcagni’ & Tiemo J. Klisch & Lorenzo Brunetti & Kangho Ho Kim & Marco De Giorgi & Ayrea Hurley & Annamaria Carissimo & Margherita Mutarelli & , 2020. "TFEB regulates murine liver cell fate during development and regeneration," Nature Communications, Nature, vol. 11(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-16300-x
    DOI: 10.1038/s41467-020-16300-x
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    Cited by:

    1. Elena Astanina & Gabriella Doronzo & Davide Corà & Francesco Neri & Salvatore Oliviero & Tullio Genova & Federico Mussano & Emanuele Middonti & Edoardo Vallariello & Chiara Cencioni & Donatella Valdem, 2022. "The TFEB-TGIF1 axis regulates EMT in mouse epicardial cells," Nature Communications, Nature, vol. 13(1), pages 1-20, December.

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