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Updated: Jul 24, 2025
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Hepatic Progenitor Specification from Pluripotent Stem Cells using a Defined Differentiation System
Published on: May 10, 2020
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An extended transcription factor regulatory network controls hepatocyte identity
Julie Dubois-Chevalier1, Céline Gheeraert1, Alexandre Berthier1
1Univ. Lille, Inserm, CHU Lille, Institut Pasteur de Lille, U1011-EGID, Lille, France.
EMBO Reports
|July 10, 2023
Summary
Hepatocyte identity relies on more than core transcription factors (TFs). A broader network, including hepatocyte identity (Hep-ID)CONNECT TFs, fine-tunes TF expression and restores identity in dedifferentiated cells.
Area of Science:
- Molecular Biology
- Genetics
- Cell Biology
Background:
- Cell identity is primarily governed by core transcriptional regulatory circuitry (CoRC).
- This CoRC typically comprises a limited set of interconnected, cell-specific transcription factors (TFs).
- The complexity of transcriptional regulation in maintaining cell identity is an area of ongoing research.
Purpose of the Study:
- To investigate the broader transcriptional regulatory network controlling hepatocyte identity beyond the core circuitry.
- To identify non-cell-specific TFs that functionally interact with the core hepatocyte regulatory network.
- To elucidate the role of these extended TF networks in maintaining and restoring hepatocyte identity.
Main Methods:
- Mining of global hepatic transcription factor (TF) regulons.
- Analysis of functional interconnections between cell-specific and non-cell-specific TFs.
- Investigation of TF roles in homeostatic conditions and in dedifferentiated hepatocytes.
Main Results:
- Hepatocyte identity is controlled by an extended network of TFs, including non-cell-specific hepatocyte identity (Hep-ID)CONNECT TFs.
- Hep-IDCONNECT TFs exhibit reciprocal transcriptional regulation with core TFs.
- Hep-IDCONNECT TFs fine-tune core TF expression, including rhythmic patterns, and can reset core TF expression in dedifferentiated hepatocytes.
Conclusions:
- Hepatocyte identity is maintained by a complex regulatory network extending beyond the core transcriptional regulatory circuitry.
- Hep-IDCONNECT TFs play a crucial role in both homeostatic regulation and the restoration of hepatocyte identity.
- This extended network provides new insights into the mechanisms governing cell-specific gene expression and identity maintenance.
Keywords:
cell identitycore regulatory networkhepatocyte dedifferentiationliver diseasetranscription factorsMore Related Videos
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