Subversion of the T/B Lineage Decision in the Thymus by Lunatic Fringe-Mediated Inhibition of Notch-1
Open accessAbstract
Notch-1 signaling is essential for lymphoid progenitors to undergo T cell commitment, but the mechanism has not been defined. Here we show that thymocytes ectopically expressing Lunatic Fringe, a modifier of Notch-1 signaling, induce lymphoid progenitors to develop into B cells in the thymus. This cell fate switch resulted from Lunatic Fringe-mediated inhibition of Notch-1 function, as revealed by experiments utilizing lymphoid progenitors in which Notch-1 activity was genetically manipulated. These data identify Lunatic Fringe as a potent regulator of Notch-1 during the T/B lineage decision and show that an important function of Notch-1 in T cell commitment is to suppress B cell development in the thymus.
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Notch activated target genes like Hes1 are expressed throughout pro-T cell phases (ETP to DN3) until TCR gene rearrangement.
“Notch activated target genes like Hes1 are expressed throughout the pro-T cell phases (ETP to DN3), until T-cell receptor (TCR) gene rearrangement (62–64)”
From Mechanisms of Action of Hematopoietic Transcription Factor PU.1 in Initiation of T-Cell Development (2019) · cites this paper as [62]
The paper’s Plasmids passage reports that activated Notch induced an HES-1 promoter reporter in NIH 3T3 cells. It does not report endogenous Hes1 expression throughout the ETP-to-DN3 pro-T phases or establish TCR gene rearrangement as its endpoint; searches for those stages and rearrangement found no such result. (LLM, conf=0.83)
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Cites
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Prethymic T‐cell development defined by the expression of paired immunoglobulin‐like receptors
Masuda, K., Kubagawa, H., Ikawa, T., Chen, C., Kakugawa, K., Hattori, M., Kageyama, R., Cooper, M. D., Minato, N., Katsura, Y., et al. (2005) · The EMBO Journal · doi:10.1038/sj.emboj.7600878 · Cited by 79 · see citing works
- Authors
- Koch, U., Lacombe, T. A., Holland, D., Bowman, J. L., Cohen, B. L., Egan, S. E., & Guidos, C. J.
- Affiliations
- University of Toronto (CA)
- Corresponding author
- Guidos, Cynthia J
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2001-08
- Volume
- 15
- Issue
- 2
- Pages
- 225-236
- ISSN
- 1074-7613 (ISSN-L)
- OpenAlex
- W2044766358
- Cited by
- 193
- References
- 1
- Citations by year
- 2025: 1 · 2024: 2 · 2023: 3 · 2022: 3 · 2021: 3 · 2020: 2 · 2019: 3 · 2018: 4 · 2017: 2 · 2016: 5 · 2015: 4 · 2014: 4 · 2013: 3 · 2012: 11
- FWCI
- 8.90
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Immunity (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University of British Columbia
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- lunatic fringe, Notch1 signaling, T cell development, T cell commitment, B cell development, lymphoid progenitors, cell fate transitions, Notch signaling inhibition
- MeSH terms
- Animals, B-Lymphocytes, Bone Marrow Cells, Cell Differentiation, Membrane Proteins, Mice, Transgenic, Proteins, Receptors, Cell Surface, Recombinant Proteins, T-Lymphocytes, Thymus Gland, Transcription Factors, Glycosyltransferases, Models, Immunological, Cell Lineage, Mice, Receptor, Notch1
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