دورية أكاديمية
Ehf and Fezf2 regulate late medullary thymic epithelial cell and thymic tuft cell development.
العنوان: | Ehf and Fezf2 regulate late medullary thymic epithelial cell and thymic tuft cell development. |
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المؤلفون: | Lammers S; Institute for Theoretical Physics, Heidelberg University, Heidelberg, Germany., Barrera V; Bioinformatics Core, Harvard T.H. Chan School of Public Health, Boston, MA, United States., Brennecke P; Department of Genetics, Stanford University, School of Medicine, Stanford, CA, United States.; Stanford Genome Technology Center, Stanford University, Stanford, CA, United States., Miller C; Diabetes Center, University of California, San Francisco (UCSF), San Francisco, CA, United States., Yoon J; Bioinformatics Core, Harvard T.H. Chan School of Public Health, Boston, MA, United States., Balolong J; Diabetes Center, University of California, San Francisco (UCSF), San Francisco, CA, United States., Anderson MS; Diabetes Center, University of California, San Francisco (UCSF), San Francisco, CA, United States., Ho Sui S; Bioinformatics Core, Harvard T.H. Chan School of Public Health, Boston, MA, United States., Steinmetz LM; Department of Genetics, Stanford University, School of Medicine, Stanford, CA, United States.; Stanford Genome Technology Center, Stanford University, Stanford, CA, United States.; Genome Biology Unit, European Molecular Biology Laboratory (EMBL), Heidelberg, Germany., von Andrian UH; Department of Immunology & HMS Center for Immune Imaging, Harvard Medical School, Boston, MA, United States.; The Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, United States., Rattay K; Department of Immunology & HMS Center for Immune Imaging, Harvard Medical School, Boston, MA, United States.; Pharmacological Institute, Biochemical Pharmacological Center, University of Marburg, Marburg, Germany. |
المصدر: | Frontiers in immunology [Front Immunol] 2024 Feb 14; Vol. 14, pp. 1277365. Date of Electronic Publication: 2024 Feb 14 (Print Publication: 2023). |
نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't; Research Support, N.I.H., Extramural |
اللغة: | English |
بيانات الدورية: | Publisher: Frontiers Research Foundation] Country of Publication: Switzerland NLM ID: 101560960 Publication Model: eCollection Cited Medium: Internet ISSN: 1664-3224 (Electronic) Linking ISSN: 16643224 NLM ISO Abbreviation: Front Immunol Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: [Lausanne : Frontiers Research Foundation] |
مواضيع طبية MeSH: | Tuft Cells* , Transcription Factors*/metabolism, Gene Expression Regulation ; Epithelial Cells/metabolism ; Peptides/metabolism |
مستخلص: | Thymic epithelial cells are indispensable for T cell maturation and selection and the induction of central immune tolerance. The self-peptide repertoire expressed by medullary thymic epithelial cells is in part regulated by the transcriptional regulator Aire (Autoimmune regulator) and the transcription factor Fezf2. Due to the high complexity of mTEC maturation stages (i.e., post-Aire, Krt10+ mTECs, and Dclk1+ Tuft mTECs) and the heterogeneity in their gene expression profiles (i.e., mosaic expression patterns), it has been challenging to identify the additional factors complementing the transcriptional regulation. We aimed to identify the transcriptional regulators involved in the regulation of mTEC development and self-peptide expression in an unbiased and genome-wide manner. We used ATAC footprinting analysis as an indirect approach to identify transcription factors involved in the gene expression regulation in mTECs, which we validated by ChIP sequencing. This study identifies Fezf2 as a regulator of the recently described thymic Tuft cells (i.e., Tuft mTECs). Furthermore, we identify that transcriptional regulators of the ELF, ESE, ERF, and PEA3 subfamily of the ETS transcription factor family and members of the Krüppel-like family of transcription factors play a role in the transcriptional regulation of genes involved in late mTEC development and promiscuous gene expression. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2024 Lammers, Barrera, Brennecke, Miller, Yoon, Balolong, Anderson, Ho Sui, Steinmetz, von Andrian and Rattay.) |
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معلومات مُعتمدة: | R01 AI155865 United States AI NIAID NIH HHS; R37 AI097457 United States AI NIAID NIH HHS; P01 HG000205 United States HG NHGRI NIH HHS; R01 GM068717 United States GM NIGMS NIH HHS |
فهرسة مساهمة: | Keywords: Ehf; Fezf2; Tuft cells; central tolerance; medullary thymic epithelial cell; thymus |
المشرفين على المادة: | 0 (Transcription Factors) 0 (Peptides) |
تواريخ الأحداث: | Date Created: 20240229 Date Completed: 20240301 Latest Revision: 20240725 |
رمز التحديث: | 20240726 |
مُعرف محوري في PubMed: | PMC10901246 |
DOI: | 10.3389/fimmu.2023.1277365 |
PMID: | 38420512 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1664-3224 |
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DOI: | 10.3389/fimmu.2023.1277365 |