Glucose modulates IRF6 transcription factor dimerization to enable epidermal differentiation

IF 19.8 1区医学 Q1 CELL & TISSUE ENGINEERING

Cell stem cell Pub Date : 2025-03-21 DOI:10.1016/j.stem.2025.02.017

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, Albert M. Li, Alan Sheng-Hwa Tung, Ronald L. Shanderson, Marten C.G. Winge, Lindsey M. Meservey, Suhas Srinivasan, Robin M. Meyers, Angela Guerrero, Andrew L. Ji, Omar S. Garcia, Paul A. Khavari

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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.

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来源期刊

Cell stem cell 生物-细胞生物学

CiteScore

37.10

自引率

2.50%

发文量

151

审稿时长

42 days

期刊介绍： Cell Stem Cell is a comprehensive journal covering the entire spectrum of stem cell biology. It encompasses various topics, including embryonic stem cells, pluripotency, germline stem cells, tissue-specific stem cells, differentiation, epigenetics, genomics, cancer stem cells, stem cell niches, disease models, nuclear transfer technology, bioengineering, drug discovery, in vivo imaging, therapeutic applications, regenerative medicine, clinical insights, research policies, ethical considerations, and technical innovations. The journal welcomes studies from any model system providing insights into stem cell biology, with a focus on human stem cells. It publishes research reports of significant importance, along with review and analysis articles covering diverse aspects of stem cell research.