Construction of developmental lineage relationships in the mouse mammary gland by single-cell RNA profiling Academic Article uri icon

abstract

  • The mammary epithelium comprises two primary cellular lineages, but the degree of heterogeneity within these compartments and their lineage relationships during development remain an open question. Here we report single-cell RNA profiling of mouse mammary epithelial cells spanning four developmental stages in the post-natal gland. Notably, the epithelium undergoes a large-scale shift in gene expression from a relatively homogeneous basal-like program in pre-puberty to distinct lineage-restricted programs in puberty. Interrogation of single-cell transcriptomes reveals different levels of diversity within the luminal and basal compartments, and identifies an early progenitor subset marked by CD55. Moreover, we uncover a luminal transit population and a rare mixed-lineage cluster amongst basal cells in the adult mammary gland. Together these findings point to a developmental hierarchy in which a basal-like gene expression program prevails in the early post-natal gland prior to the specification of distinct lineage signatures, and the presence of cellular intermediates that may serve as transit or lineage-primed cells.

authors

  • Pal, Bhupinder
  • Chen, Yunshun
  • Vaillant, François
  • Jamieson, Paul
  • Gordon, Lavinia
  • Rios, Anne C
  • Wilcox, Stephen
  • Fu, Naiyang
  • Liu, Kevin He
  • Jackling, Felicity C
  • Davis, Melissa J
  • Lindeman, Geoffrey J
  • Smyth, Gordon K
  • Visvader, Jane E

publication date

  • 2017