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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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The T and B lymphocytes of the adaptive immune system develop from common lymphoid progenitor cells in the bone marrow. These progenitors give rise to precursors that eventually develop into both T and B lymphocytes. As these precursors mature, they gain the ability to detect and respond to foreign antigens in the body, a process known as immunocompetence. Additionally, these precursors acquire self-tolerance, a process that ensures they do not react to self-antigens. This intricate system...
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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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The innate immune response is an immediate and non-specific response against pathogens, acting swiftly to prevent the spread of infections. The primary cells involved in this response are phagocytes and natural killer (NK) cells.
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Related Experiment Video

Updated: Dec 6, 2025

Isolation of Group 2 Innate Lymphoid Cells from Mouse Nasal Mucosa to Detect the Expression of CD226
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Notch Regulates Innate Lymphoid Cell Plasticity during Human NK Cell Development.

Ansel P Nalin1,2, Jesse J Kowalski1, Alexander C Sprague1

  • 1Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210.

Journal of Immunology (Baltimore, Md. : 1950)
|October 6, 2020
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Summary

Notch signaling in human tonsil NK cell developmental intermediates (NKDIs) directs cell fate. Notch activation promotes non-NK cell differentiation in early stages but is required for NK cell maturation in later stages.

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Area of Science:

  • Immunology
  • Developmental Biology
  • Cell Biology

Background:

  • Human Natural Killer (NK) cells originate from distinct NK cell developmental intermediates (NKDIs) within tonsils.
  • The precise molecular mechanisms governing NKDI differentiation and lineage commitment remain largely unknown.

Purpose of the Study:

  • To investigate the role of Notch signaling in regulating human NK cell development and differentiation from NKDIs.
  • To determine stage-specific effects of Notch activation on NKDI plasticity and functional maturation.

Main Methods:

  • Utilized human tonsil-derived NKDIs at distinct developmental stages (Stage 3, 4A, 4B).
  • Investigated the impact of Notch activation, in conjunction with OP9 stromal cells, on NKDI differentiation pathways.
  • Analyzed NK cell lineage commitment, non-NK innate lymphoid cell differentiation, and NK cell functional maturation markers (e.g., NKp80 expression).

Main Results:

  • Notch activation in Stage 3 and 4A NKDIs promoted non-NK innate lymphoid cell differentiation, inhibiting NK cell development.
  • Stage 4B NKDIs demonstrated NK cell lineage commitment, irrespective of Notch activation.
  • Notch signaling was essential for NKp80 expression and a Stage 4B-like phenotype in mature NK cells derived from earlier stages.
  • Notch-dependent effects were stage-specific, involving NOTCH1 and NOTCH2 in Stage 3 and primarily NOTCH1 in Stage 4A NKDIs.

Conclusions:

  • Notch signaling plays a critical, stage-specific role in regulating the developmental plasticity of human NK cells.
  • Stromal cell interactions are crucial for mediating Notch-dependent effects on NK cell development.
  • Understanding these mechanisms provides insights into the intricate regulation of human NK cell maturation.