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Mammosphere Formation Assay from Human Breast Cancer Tissues and Cell Lines
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Published on: March 22, 2015

Stem cells and the mammary microenvironment.

Brian W Booth1, Corinne A Boulanger, Gilbert H Smith

  • 1Section for Mammary Stem Cell Biology, Mammary Biology and Tumorigenesis Laboratory, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.

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Mouse mammary glands can regenerate from a single cell, revealing three distinct progenitor cell types. The mammary microenvironment influences stem cell fate, suggesting environmental factors are crucial for tissue development and regeneration.

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Area of Science:

  • Developmental Biology
  • Stem Cell Biology
  • Epithelial Biology

Background:

  • Mammary epithelial outgrowths can arise from a single progenitor cell.
  • Retroviral insertion sites confirm clonal origin in successive transplant generations.
  • Three distinct mammary epithelial progenitors (duct-limited, lobule-limited, and complete) have been identified in mice.

Purpose of the Study:

  • To investigate the clonal origin and regenerative capacity of mammary epithelial progenitors.
  • To characterize the self-renewal and differentiation potential of identified progenitor cells.
  • To explore the influence of the mammary microenvironment on stem cell fate determination.

Main Methods:

  • Mammary fragment transplantation and limiting dilution analysis.
  • Cre-lox conditional activation of reporter genes (lacZ) for lineage tracing.
  • In vivo transplantation of genetically marked cells into epithelium-divested mammary fat pads.

Main Results:

  • Transplantation studies identified three distinct mammary epithelial progenitors.
  • Lobule-limited progenitors were lineage-marked and shown to regenerate secretory lobules across pregnancies.
  • Cells from other tissues, when placed in the mammary microenvironment, adopted mammary epithelial cell fates.

Conclusions:

  • The mouse mammary gland contains at least three distinct epithelial progenitor populations.
  • The mammary microenvironment plays a dominant role in directing the cell fate of resident stem cells.
  • Somatic stem cell plasticity is influenced by extrinsic environmental cues in vivo.