A stage-specific enhancer augments Notch1 signaling from the early thymic progenitor (ETP) through double-negative thymocyte stages. Enhanced Notch1 activity is required for T cell lineage differentiation at the later end of this developmental interval, but Notch1 also suppresses precocious T lineage commitment in ETPs and promotes their expansion as multi-lineage progenitors.
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References
Koch, U. & Radtke, F. Mechanisms of T cell development and transformation. Annu. Rev. Cell. Dev. Biol. 27, 539–562 (2011). A Review article that discusses the role of Notch1 signaling in T cell development and leukemogenesis.
Gomez del Arco, P. et al. Alternative promoter usage at the Notch1 locus supports ligand-independent signaling in T cell development and leukemogenesis. Immunity 33, 685–698 (2010). This paper reports a regulatory region upstream of the Notch1 promoter that is active during thymic progenitor development and supports both Notch1 expression and T cell leukemogenesis, even after deletion of the canonical Notch1 promoter.
Feyerabend, T. B. et al. Deletion of Notch1 converts pro-T cells to dendritic cells and promotes thymic B cells by cell-extrinsic and cell-intrinsic mechanisms. Immunity 30, 67–79 (2009). This paper reports that a T cell progenitor-specific Notch1 null mutation causes accumulation of B cells and dendritic cells in the thymus, indicating that Notch1 signaling restricts non-T-cell lineage potential.
Thompson, P. K. & Zuniga-Pflucker, J. C. On becoming a T cell, a convergence of factors kick it up a Notch along the way. Semin. Immunol. 23, 350–359 (2011). A Review article that discusses the role of transcription factors and Notch1 signaling in early T cell development.
Zhou, W. et al. Single-cell analysis reveals regulatory gene expression dynamics leading to lineage commitment in early T cell development. Cell Syst. 9, 321–337 (2019). This paper uses single-cell profiling approaches to investigate early T cell differentiation in the thymus.
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This is a summary of: Georgopoulos, K. et al. A double-negative thymocyte specific enhancer augments Notch1 signaling to direct early T cell progenitor expansion, lineage restriction and β-selection. Nat. Immunol. https://doi.org/10.1038/s41590-022-01322-y (2021).
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Notch gives early T cell progenitors time to grow up. Nat Immunol 23, 1523–1524 (2022). https://doi.org/10.1038/s41590-022-01323-x
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DOI: https://doi.org/10.1038/s41590-022-01323-x
