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Updated: Jun 28, 2026
11:13
Indirect Immunofluorescence on Frozen Sections of Mouse Mammary Gland
Published on: December 1, 2015
Notch signaling regulates mammary stem cell function and luminal cell-fate commitment.
Toula Bouras1, Bhupinder Pal, François Vaillant
1VBCRC Laboratory, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3050, Australia.
Cell Stem Cell
|October 23, 2008
Summary
Notch signaling restricts mammary stem cell (MaSC) expansion and promotes luminal lineage commitment. Aberrant Notch activation in progenitor cells drives hyperplasia and tumorigenesis, highlighting its critical role in mammary development and cancer.
Area of Science:
- Developmental Biology
- Stem Cell Biology
- Cancer Biology
Background:
- Recent identification of mouse mammary stem cells (MaSCs) and progenitor cells.
- Understanding the genetic control of mammary epithelial lineage specification and differentiation is crucial.
Purpose of the Study:
- To investigate the role of the Notch pathway in the mammary epithelial hierarchy.
- To determine Notch signaling's impact on mammary stem cell activity and lineage commitment.
Main Methods:
- Knockdown of the Notch effector Cbf-1 in MaSC-enriched populations.
- In vivo analysis of Notch pathway activation in mammary epithelium.
- Assessment of effects of constitutive Notch signaling on progenitor cells.
Main Results:
- Cbf-1 knockdown in MaSCs increased stem cell activity and caused aberrant end bud formation, suggesting Notch restricts MaSC expansion.
- Notch signaling was activated in ductal luminal epithelium and promoted MaSC commitment to the luminal lineage.
- Constitutive Notch signaling led to luminal progenitor cell expansion, hyperplasia, and tumorigenesis.
Conclusions:
- Notch signaling plays key roles in regulating mammary stem cells (MaSCs) and luminal cell commitment.
- Inappropriate Notch activation promotes self-renewal and transformation of luminal progenitor cells, contributing to mammary tumorigenesis.
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01:12Role Of Notch Signalling In Intestinal Stem Cell Renewal
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...
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...
03:14Notch Signaling Pathway
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 until 1985...
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 until 1985...
03:14Notch Signaling Pathway
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 until 1985...
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 until 1985...
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