Stem Cells and the Differentiation Hierarchy in Mammary Gland Development

Physiol Rev. 2020 Apr 1;100(2):489-523. doi: 10.1152/physrev.00040.2018. Epub 2019 Sep 20.

Abstract

The mammary gland is a highly dynamic organ that undergoes profound changes within its epithelium during puberty and the reproductive cycle. These changes are fueled by dedicated stem and progenitor cells. Both short- and long-lived lineage-restricted progenitors have been identified in adult tissue as well as a small pool of multipotent mammary stem cells (MaSCs), reflecting intrinsic complexity within the epithelial hierarchy. While unipotent progenitor cells predominantly execute day-to-day homeostasis and postnatal morphogenesis during puberty and pregnancy, multipotent MaSCs have been implicated in coordinating alveologenesis and long-term ductal maintenance. Nonetheless, the multipotency of stem cells in the adult remains controversial. The advent of large-scale single-cell molecular profiling has revealed striking changes in the gene expression landscape through ontogeny and the presence of transient intermediate populations. An increasing number of lineage cell-fate determination factors and potential niche regulators have now been mapped along the hierarchy, with many implicated in breast carcinogenesis. The emerging diversity among stem and progenitor populations of the mammary epithelium is likely to underpin the heterogeneity that characterizes breast cancer.

Keywords: breast cancer; mammary gland development; progenitors; stem cells; transcriptional regulators.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Cell Differentiation*
  • Cell Lineage*
  • Cell Transformation, Neoplastic / genetics
  • Cell Transformation, Neoplastic / metabolism
  • Cell Transformation, Neoplastic / pathology
  • Female
  • Gene Expression Regulation, Developmental
  • Humans
  • Mammary Glands, Animal / metabolism*
  • Mammary Glands, Animal / pathology
  • Mammary Glands, Human / metabolism*
  • Mammary Glands, Human / pathology
  • Morphogenesis
  • Neoplastic Stem Cells / metabolism
  • Neoplastic Stem Cells / pathology
  • Phenotype
  • Signal Transduction
  • Stem Cells / metabolism*
  • Stem Cells / pathology
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Tumor Microenvironment

Substances

  • Transcription Factors