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Mammosphere Formation Assay from Human Breast Cancer Tissues and Cell Lines
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Hybrid Stem Cell States: Insights Into the Relationship Between Mammary Development and Breast Cancer Using

Tasha Thong1, Yutong Wang2, Michael D Brooks3

  • 1Department of Environmental Health Sciences, School of Public Health, University of Michigan, Ann Arbor, MI, United States.

Frontiers in Cell and Developmental Biology
|May 28, 2020
PubMed
Summary
This summary is machine-generated.

Normal mammary stem cells exhibit plasticity, shifting between epithelial and mesenchymal states. Hybrid E/M cells, rare in normal tissue, are linked to breast cancer metastasis and developmental immaturity.

Keywords:
breast cancerepithelialhybridmesenchymalpregnancysingle-cell RNA sequencingstem cells

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Area of Science:

  • Developmental Biology
  • Cancer Biology
  • Stem Cell Biology

Background:

  • Mammary stem cells (MSCs) share similarities with cancer cells, implicating them in breast carcinogenesis.
  • Normal breast stem cells exist in epithelial, mesenchymal, and hybrid epithelial/mesenchymal (E/M) states.
  • Hybrid E/M cells are linked to breast cancer metastasis and poor prognosis, with phenotypes changing throughout life.

Purpose of the Study:

  • To quantify normal mammary (NM) gland cell state distributions during development and after in vitro stem-like perturbation.
  • To investigate hybrid stem cell states in normal mammary glands and cancer using integrated single-cell RNA-sequencing data.
  • To understand the relationship between hybrid cell populations, stemness, and breast cancer development.

Main Methods:

  • Single-cell RNA-sequencing (scRNA-seq) of normal mammary gland cells and conditionally reprogrammed (CR) cells.
  • Machine learning-based dataset alignment to integrate human and mouse scRNA-seq data, and TCGA bulk RNA-seq data.
  • Pseudotime analysis to infer developmental trajectories and identify hybrid cell populations.

Main Results:

  • Conditional reprogramming (CR) expands a stem cell state with increased embryonic stem cell gene expression.
  • Three rare hybrid populations (KRT18+/KRT14+, EPCAM+/VIM+, quadruple positive) emerge after CR, with E/M hybrids being most developmentally immature.
  • Hybrid E/M cells enrich during pregnancy, suggesting a role in mammary morphogenesis; breast cancer subtypes show distinct developmental signatures.

Conclusions:

  • Normal mammary stem cells display significant phenotypic plasticity, including the emergence of hybrid states.
  • Hybrid E/M cells represent a developmentally immature state, enriched during pregnancy and potentially linked to breast cancer.
  • Breast cancer subtypes reflect distinct developmental signatures, highlighting the role of stem cell plasticity in tumorigenesis.