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Related Concept Videos

Notch Signaling Pathway03:14

Notch Signaling Pathway

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The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not...
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Role Of Notch Signalling In Intestinal Stem Cell Renewal01:12

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Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
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Stem Cell Niche01:26

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The stem cell niche is the dynamic microenvironment where stem cells reside. Inside these niches, the cells may remain undifferentiated, undergo high self-renewal, or become lineage-specific progenitors. Stem cells coexist with other niche cells, such as stromal cells. They also interact closely with the ECM. Cell-cell and cell-matrix communication occur via adhesion molecules or soluble factors that signal the stem cells and determine their fate. Stromal cells also provide survival signals to...
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NF-κB-dependent Signaling Pathway02:26

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The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
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T Cell Activation and Clonal Selection01:22

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T cells are integral to our adaptive immune system, recognizing and effectively responding to foreign antigens. T cell activation and clonal selection are pivotal in orchestrating this immune response. This article elucidates these mechanisms, detailing the roles of cluster of differentiation (CD) markers, major histocompatibility complex (MHC) molecules, costimulatory signals, and the process of clonal selection.
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Related Experiment Video

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Stimulation of Notch Signaling in Mouse Osteoclast Precursors
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Notch Signaling Regulates the Homeostasis of Tissue-Restricted Innate-like T Cells.

Vijaykumar Chennupati1, Ute Koch2, Manuel Coutaz3

  • 1Ludwig Centre for Cancer Research, University of Lausanne, 1066 Epalinges, Switzerland; Swiss Vaccine Research Institute, Lausanne University Hospital, 1066 Epalinges, Switzerland; Division of Immunology and Allergy, Department of Medicine, Lausanne University Hospital, 1066 Epalinges, Switzerland; hughrobson.macdonald@unil.ch vijaykumar.chennupati@unil.ch.

Journal of Immunology (Baltimore, Md. : 1950)
|June 22, 2016
PubMed
Summary

Notch signaling is crucial for maintaining the balance of innate-like T cells, including invariant NKT cells. This pathway controls their survival and overall homeostasis through complex cellular interactions.

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Cell Aggregation Assays to Evaluate the Binding of the Drosophila Notch with Trans-Ligands and its Inhibition by Cis-Ligands
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Area of Science:

  • Immunology
  • Cell Biology
  • Developmental Biology

Background:

  • Notch signaling is vital for conventional T cell development.
  • The role of Notch signaling in innate-like T cells remains largely unexplored.

Purpose of the Study:

  • To investigate the function of Notch signaling in the homeostasis of innate-like T cells.
  • To elucidate the mechanisms by which Notch signaling regulates these specific T cell populations.

Main Methods:

  • Conditional ablation of Notch receptors and ligands in T cells and stromal cells.
  • Analysis of T cell populations including invariant NKT cells, CD8ααTCRαβ IELs, and innate memory CD8 T cells.
  • Assessment of gene expression related to cell survival (Bcl-2, IL-7Rα).

Main Results:

  • Notch signaling controls the homeostasis of hepatic invariant NKT cells, CD8ααTCRαβ IELs, and innate memory CD8 T cells.
  • Notch selectively regulates hepatic iNKT cell survival by modulating Bcl-2 and IL-7Rα expression.
  • Notch-mediated regulation involves both cell-intrinsic and extrinsic mechanisms, including interactions with fibroblastic stromal cells.

Conclusions:

  • Notch signaling is indispensable for the homeostasis of multiple tissue-restricted innate-like T cell populations.
  • These findings establish a generalized role for Notch signaling in innate T cell homeostasis.
  • Context-dependent interactions with stromal cells are critical for Notch-mediated regulation.