Evidence map›Paper›PMID 40120584›Full record

ArticleCell stem cell2025

Glucose modulates IRF6 transcription factor dimerization to enable epidermal differentiation.

Vanessa Lopez-Pajares, Aparna Bhaduri, Yang Zhao, Gayatri Gowrishankar, Laura K H Donohue, Margaret G Guo, Zurab Siprashvili, Weili Miao, Duy T Nguyen, Xue Yang and 15 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell stem cell, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

14 citing papers in PubMed.

  1. Article
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  6. Type 2 diabetes mellitus exacerbates vaginal group BbioRxiv : the preprint server for biology · 2026
    Article
  7. Regulation of RNA-binding proteins by small biomolecules.Nature reviews. Molecular cell biology · 2026
    Review
  8. Article
  9. Article
  10. Review
  11. Article
  12. Article
  13. Review
  14. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

25 authors.

Vanessa Lopez-PajaresProgram in Epithelial Biology, Stanford University School of Medicine, Stanford, CA 94305, USA. Electronic address: vlopezp@stanford.edu.
Aparna BhaduriProgram in Epithelial Biology, Stanford University School of Medicine, Stanford, CA 94305, USA; Program in Cancer Biology, Stanford University, Stanford, CA 94305, USA.
Yang ZhaoProgram in Epithelial Biology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Gayatri GowrishankarDepartments of Bioengineering and Radiology, Stanford University, Stanford, CA 94305, USA; Molecular Imaging Program at Stanford, Stanford University, Stanford, CA 94305, USA.
Laura K H DonohueProgram in Epithelial Biology, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Genetics, Stanford University, Stanford, CA 94305, USA.
Margaret G GuoProgram in Epithelial Biology, Stanford University School of Medicine, Stanford, CA 94305, USA; Program in Biomedical Informatics, Stanford University, Stanford, CA 94305, USA.
Zurab SiprashviliProgram in Epithelial Biology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Weili MiaoProgram in Epithelial Biology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Duy T NguyenProgram in Epithelial Biology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Xue YangProgram in Epithelial Biology, Stanford University School of Medicine, Stanford, CA 94305, USA; Program in Cancer Biology, Stanford University, Stanford, CA 94305, USA.
Albert M LiDepartment of Radiation Oncology, Stanford University, Stanford, CA 94305, USA.
Alan Sheng-Hwa TungDepartment of Pathology, Stanford University, Stanford, CA 94350, USA; Sarafan ChEM-H, Stanford University, Stanford, CA 94305, USA.
Ronald L ShandersonProgram in Epithelial Biology, Stanford University School of Medicine, Stanford, CA 94305, USA; Program in Cancer Biology, Stanford University, Stanford, CA 94305, USA.
Marten C G WingeProgram in Epithelial Biology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Lindsey M MeserveyProgram in Epithelial Biology, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Biology, Stanford University, Stanford, CA 94305, USA.
Suhas SrinivasanProgram in Epithelial Biology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Robin M MeyersProgram in Epithelial Biology, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Genetics, Stanford University, Stanford, CA 94305, USA.
Angela GuerreroProgram in Epithelial Biology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Andrew L JiProgram in Epithelial Biology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Omar S GarciaProgram in Epithelial Biology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Shiying TaoProgram in Epithelial Biology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Sanjiv S GambhirDepartments of Bioengineering and Radiology, Stanford University, Stanford, CA 94305, USA; Molecular Imaging Program at Stanford, Stanford University, Stanford, CA 94305, USA.
Jonathan Z LongDepartment of Pathology, Stanford University, Stanford, CA 94350, USA; Sarafan ChEM-H, Stanford University, Stanford, CA 94305, USA.
Jiangbin YeDepartment of Radiation Oncology, Stanford University, Stanford, CA 94305, USA.
Paul A KhavariProgram in Epithelial Biology, Stanford University School of Medicine, Stanford, CA 94305, USA; Program in Cancer Biology, Stanford University, Stanford, CA 94305, USA; Veterans Affairs Palo Alto Healthcare System, Palo Alto, CA 94304, USA. Electronic address: khavari@stanford.edu.

Funding

Translational Oncology Research Program (Project-005)P30CA124435 · NCI · STANFORD UNIVERSITY · PI Vittorio Sebastiano · 2007 to 2026
$71.4M
Leveraging innovative technologies in basic and clinical cancer researchT32CA009302 · NCI · STANFORD UNIVERSITY · PI LAURA D ATTARDI, Aaron M Newman · 1985 to 2026
$19.1M
REGULATORS OF EPIDERMAL GENE EXPRESSIONR01AR045192 · NIAMS · STANFORD UNIVERSITY · PI PAUL KHAVARI · 1999 to 2026
$9.9M
Mechanisms of Epidermal Homeostasis and Early NeoplasiaR01AR043799 · NIAMS · STANFORD UNIVERSITY · PI PAUL KHAVARI · 1998 to 2026
$9.1M
Transcriptional Regulatory Complexes in Epidermal DifferentiationK01AR070895 · NIAMS · STANFORD UNIVERSITY · PI LOPEZPAJARES, VANESSA · 2017 to 2022
$709k
BLRD VA I01 BX001409NCI NIH HHS P30 CA124435NCI NIH HHS T32 CA009302NIAMS NIH HHS K01 AR070895NIAMS NIH HHS R01 AR043799NIAMS NIH HHS R01 AR045192
6 · The paper itself

Abstract

Non-energetic roles for glucose are largely unclear, as is the interplay between transcription factors (TFs) and ubiquitous biomolecules. Metabolomic analyses uncovered elevation of intracellular glucose during differentiation of diverse cell types. Human and mouse tissue engineered with glucose sensors detected a glucose gradient that peaked in the outermost differentiated layers of the epidermis. Free glucose accumulation was essential for epidermal differentiation and required the SGLT1 glucose transporter. Glucose affinity chromatography uncovered glucose binding to diverse regulatory proteins, including the IRF6 TF. Direct glucose binding enabled IRF6 dimerization, DNA binding, genomic localization, and induction of IRF6 target genes, including essential pro-differentiation TFs GRHL1, GRHL3, HOPX, and PRDM1. These data identify a role for glucose as a gradient morphogen that modulates protein multimerization in cellular differentiation.

Indexed as

Cell DifferentiationEpidermal CellsEpidermisGlucoseInterferon Regulatory FactorsProtein MultimerizationAnimalsHumansMiceTranscription FactorsGlucoseInterferon Regulatory FactorsTranscription FactorsdifferentiationglucoseIRF6

Identifiers

PMID40120584
PMCPMC12048241

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.