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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.
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
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Lineage Commitment01:21

Lineage Commitment

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Commitment is the  process whereby stem cells:
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TGF - β Signaling Pathway01:16

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The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
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Inheritance of Chromatin Structures03:17

Inheritance of Chromatin Structures

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Epigenetics is the study of inherited changes in a cell's phenotype without changing the DNA sequences. It provides a form of memory for the differential gene expression pattern to maintain cell lineage, position-effect variegation, dosage compensation, and maintenance of chromatin structures such as telomeres and centromeres. For example, the structure and location of the centromere on chromosomes are epigenetically inherited. Its functionality is not dictated or ensured by the underlying...
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Canonical Wnt Signaling Pathway02:54

Canonical Wnt Signaling Pathway

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The gene encoding the main signaling molecules of the Wnt signaling pathways (the Wnt proteins) was discovered almost four decades ago by Nüsslein-Volhard and Wieschaus. They identified and originally named the gene "wingless" (wg) after a phenotype discovered during their landmark genetic screen in Drosophila for body pattern defects. At around the same time, another researcher named Harold Varmus found that a murine tumor virus activates the mammalian wg homolog, Int-1, which...
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Related Experiment Video

Updated: Jan 9, 2026

Stimulation of Notch Signaling in Mouse Osteoclast Precursors
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Notch interaction with RUNX factors regulates initiation of the T-lineage program.

Yuichi Kama1, Ken-Ichi Hirano1, Kaori Masuhara1,2

  • 1Department of Immunology, Tokai University School of Medicine, Isehara, Japan.

The Journal of Experimental Medicine
|December 4, 2025
PubMed
Summary

Runt-related transcription factor 1 (RUNX1) changes its partners during T cell development. Initially binding CCCTC-binding factor (CTCF), it later partners with Notch1, altering gene expression to initiate T-cell programs.

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Investigation of the Transcriptional Role of a RUNX1 Intronic Silencer by CRISPR/Cas9 Ribonucleoprotein in Acute Myeloid Leukemia Cells
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Real-time Bioluminescence Imaging of Notch Signaling Dynamics during Murine Neurogenesis
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Investigation of the Transcriptional Role of a RUNX1 Intronic Silencer by CRISPR/Cas9 Ribonucleoprotein in Acute Myeloid Leukemia Cells
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Area of Science:

  • Immunology
  • Molecular Biology
  • Cell Biology

Background:

  • Runt-related transcription factors (RUNX) are crucial for T cell development.
  • RUNX1 undergoes dynamic partner switching at the T-lineage commitment checkpoint.
  • Understanding RUNX factor function at different T cell progenitor stages is essential.

Purpose of the Study:

  • To investigate the functional differences of RUNX factors between lymphoid progenitor (LP) and Notch-stimulated T progenitor stages (Phase 1).
  • To identify RUNX1-interacting partners specific to LP and Phase 1 stages.
  • To elucidate the role of these complexes in regulating T-cell gene expression.

Main Methods:

  • Utilized CRISPR/Cas9 for stage-specific deletion of RUNX factors and binding partners.
  • Identified RUNX1-interacting partners using co-immunoprecipitation and genomic analysis.
  • Analyzed the impact of identified complexes on T-signature gene expression.

Main Results:

  • CCCTC-binding factor (CTCF) was identified as an LP-specific RUNX1-interacting partner.
  • Notch1 intracellular domain directly interacts with RUNX1 in Phase 1, recruiting a Mediator/p300 complex.
  • The RUNX1/CTCF complex negatively regulates T-signature genes in LP, while the RUNX1/Mediator/p300 complex promotes their expression in Phase 1.

Conclusions:

  • Notch-mediated functional conversion of RUNX factors is critical for initiating the T-lineage program.
  • RUNX1 undergoes protein complex reorganization and genomic redeployment during T cell development.
  • Dynamic regulation of RUNX1 complexes dictates its role in T-cell commitment and differentiation.