Essential role for a novel population of binucleated mammary epithelial cells in lactation

Nat Commun. 2016 Apr 22:7:11400. doi: 10.1038/ncomms11400.

Abstract

The mammary gland represents a unique tissue to study organogenesis as it predominantly develops in the post-natal animal and undergoes dramatic morphogenetic changes during puberty and the reproductive cycle. The physiological function of the mammary gland is to produce milk to sustain the newborn. Here we view the lactating gland through three-dimensional confocal imaging of intact tissue. We observed that the majority of secretory alveolar cells are binucleated. These cells first arise in very late pregnancy due to failure of cytokinesis and are larger than mononucleated cells. Augmented expression of Aurora kinase-A and Polo-like kinase-1 at the lactogenic switch likely mediates the formation of binucleated cells. Our findings demonstrate an important physiological role for polyploid mammary epithelial cells in lactation, and based on their presence in five different species, suggest that binucleated cells evolved to maximize milk production and promote the survival of offspring across all mammalian species.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aurora Kinase A / genetics*
  • Aurora Kinase A / metabolism
  • Breast Feeding
  • Cell Cycle Proteins / genetics*
  • Cell Cycle Proteins / metabolism
  • Cell Differentiation
  • Cell Nucleus / ultrastructure
  • Cell Size
  • Cytokinesis / genetics
  • Epithelial Cells / metabolism*
  • Epithelial Cells / ultrastructure
  • Female
  • Gene Expression Regulation, Developmental
  • Humans
  • Lactation / physiology*
  • Mammary Glands, Animal / metabolism*
  • Mammary Glands, Animal / ultrastructure
  • Mammary Glands, Human / metabolism*
  • Mammary Glands, Human / ultrastructure
  • Mice
  • Mice, Transgenic
  • Milk / metabolism
  • Milk / physiology
  • Polo-Like Kinase 1
  • Pregnancy
  • Primary Cell Culture
  • Protein Serine-Threonine Kinases / genetics*
  • Protein Serine-Threonine Kinases / metabolism
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins / metabolism

Substances

  • Cell Cycle Proteins
  • Proto-Oncogene Proteins
  • AURKA protein, human
  • Aurora Kinase A
  • Protein Serine-Threonine Kinases