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Cited by 49Gene Regulatory Network AnalysisGenomics and Chromatin DynamicsDevelopmental Biology and Gene Regulation

Employing core regulatory circuits to define cell identity

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Almeida, Nathalia, Chung, Matthew W H, Drudi, Elena M, Engquist, Elise N, Hamrud, Eva, Isaacson, Abigail, Tsang, Victoria S K, Watt, Fiona M +1 more·2021·The EMBO Journal
DOI 10.15252/embj.2020106785PMC PMC8126924
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Abstract

The interplay between extrinsic signaling and downstream gene networks controls the establishment of cell identity during development and its maintenance in adult life. Advances in next-generation sequencing and single-cell technologies have revealed additional layers of complexity in cell identity. Here, we review our current understanding of transcription factor (TF) networks as key determinants of cell identity. We discuss the concept of the core regulatory circuit as a set of TFs and interacting factors that together define the gene expression profile of the cell. We propose the core regulatory circuit as a comprehensive conceptual framework for defining cellular identity and discuss its connections to cell function in different contexts.

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  • A limited set of identity transcription factors engaging in auto- and cross-regulatory loops typically defines the core transcriptional regulatory circuitry (CoRC).

    “A limited set of identity TFs engaging into auto‐ and cross‐regulatory loops typically defines the core transcriptional regulatory circuitry (CoRC; Arendt et al, 2016; Almeida et al, 2021).”

    From An extended transcription factor regulatory network controls hepatocyte identity (2023) · cites this paper as Almeida et al, 2021

    The Introduction assigns the small set of transcription factors and their auto- and cross-regulatory loops to core regulatory circuitry (CRC). It defines CoRC separately as a core regulatory complex involving the physical cooperativity of terminal selectors. The citing sentence conflates these distinct terms. (LLM, conf=0.88)

    Checked by a reasoning model — may be wrong.

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  • Cell-specific transcription factors directly control the expression of non-transcription-factor genes that exert activities/functions characterizing individual cell types (identity effector genes).

    “cell‐specific TFs directly control the expression of non‐TF genes exerting activities/functions characterizing individual cell‐types, alternatively known as identity effector genes (Arendt et al, 2016; Almeida et al, 2021).”

    From An extended transcription factor regulatory network controls hepatocyte identity (2023) · cites this paper as Almeida et al, 2021

  • The moderate transcriptional changes most probably relate to the intrinsic role of identity transcription factor networks, which are built up to allow robustness of individual cell-type transcriptional programs.

    “This most probably relates to the intrinsic role of identity TF networks, which are built‐up to allow robustness of individual cell‐type transcriptional programs (Kyrmizi et al, 2006; Almeida et al, 2021).”

    From An extended transcription factor regulatory network controls hepatocyte identity (2023) · cites this paper as Almeida et al, 2021

  • Core transcriptional regulatory circuitries are considered cornerstones for establishment and maintenance of cell identities.

    “CoRCs are considered cornerstones for establishment and maintenance of cell identities (Arendt et al, 2016; Almeida et al, 2021).”

    From An extended transcription factor regulatory network controls hepatocyte identity (2023) · cites this paper as Almeida et al, 2021

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Cited by

Sorted by citations

  • An extended transcription factor regulatory network controls hepatocyte identity

    Dubois‐Chevalier, J., Gheeraert, C., Berthier, A., Boulet, C., Dubois, V., Guille, L., Fourcot, M., Marot, G., Gauthier, K., Dubuquoy, L., et al. (2023) · EMBO Reports · doi:10.15252/embr.202357020 · Cited by 6 · see citing works

    “…to self-sustain high expression of identity TFs and their target effector genes in addition to being involved in the continuous modulation of the hepatic transcriptome in response to environmental stimuli (Boyer et al , 2005; Arendt et al , 2016; Wilkinson et al , 2017; Almeida et al , 2021).”
    Influential

Authors
Almeida, N., Chung, M. W. H., Drudi, E. M., Engquist, E. N., Hamrud, E., Isaacson, A., Tsang, V. S. K., Watt, F. M., & Spagnoli, F. M.
Affiliations
Guy's Hospital (GB)
Corresponding author
  • Watt, Fiona M
  • Spagnoli, Francesca M
ORCID
Venue
The EMBO Journal
Publisher
Springer Science and Business Media LLC
Published
2021-05-02
Volume
40
Issue
10
Pages
e106785-e106785
ISSN
  • 0261-4189 (ISSN-L)
  • 1460-2075
DOI
10.15252/embj.2020106785
PMC
PMC8126924
OpenAlex
W3157806418
Cited by
49
References
15
Citations by year
2026: 8 · 2025: 8 · 2024: 14 · 2023: 9 · 2022: 6 · 2021: 4
FWCI
0.87
Type
journal article
Language
en
Open access
Licence
Locations
  • The EMBO Journal (publishedVersion, other-oa)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Research Portal (King's College London) (submittedVersion, cc-by)
Funders
Wellcome Trust (108874/Z/15/Z)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene Regulatory Network Analysis
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
Keywords
cell identity, transcriptional regulatory networks, transcription factors, gene regulatory networks, extrinsic signaling, cell fate determination, gene expression profiles, single-cell technologies
MeSH terms
Humans, Transcription Factors, Regenerative Medicine

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