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After cellular or tissue damage, the resident stem cells present in the human body can locally repair and regenerate the damaged tissue or organ. However, even though some tissues do not have stem cells, they can repair and regenerate with the help of pre-existing cells. For example, beta cells of the pancreas and hepatocytes of the liver can divide to renew and regenerate the tissue. Here, both cell division and cell death are well regulated by homeostasis.
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Integrin-Rac signalling for mammary epithelial stem cell self-renewal.

Safiah Olabi1, Ahmet Ucar1, Keith Brennan1

  • 1Wellcome Centre for Cell-Matrix Research and Manchester Breast Centre, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, M13 9PT, UK.

Breast Cancer Research : BCR
|October 24, 2018
PubMed
Summary

Integrins are crucial for mammary stem cell self-renewal. This study reveals integrin signaling activates Rac1 and Wnt pathways, essential for maintaining mammary stem cell populations.

Keywords:
Mammary epithelial cellsRac1Stem cellsWntβ1-integrin

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Area of Science:

  • Cell Biology
  • Developmental Biology
  • Stem Cell Research

Background:

  • Mammary epithelial stem cells are precursors for all mammary cell types.
  • Integrins, as extracellular matrix receptors, are vital for mammary epithelial development and function.
  • Previous work established integrins' role in mammary epithelial cell survival, cell cycle, polarity, and gene expression.

Purpose of the Study:

  • To investigate the role of integrins in mammary epithelial stem cell self-renewal.
  • To elucidate the molecular mechanisms by which integrins influence mammary stem cell maintenance.

Main Methods:

  • Utilized an in vitro stem cell assay with primary mouse mammary epithelial cells.
  • Employed a 3D organoid assay to differentiate stem cell-driven (solid) and progenitor-driven (hollow) organoids.

Main Results:

  • Demonstrated that integrins are essential for the maintenance and self-renewal of mammary epithelial stem cells.
  • Showed that integrins activate the Rac1 signaling pathway in stem cells.
  • Identified that Rac1 activation stimulates a Wnt pathway, leading to the expression of β-catenin target genes (e.g., Axin2, Lef1).

Conclusions:

  • Integrin/Rac signaling is critical for mammary epithelial stem cell self-renewal.
  • This signaling pathway specifies the activation of a canonical Wnt pathway necessary for stem cell maintenance.