AP-2γ Is Required for Maintenance of Multipotent Mammary Stem Cells

Stem Cell Reports. 2021 Jan 12;16(1):106-119. doi: 10.1016/j.stemcr.2020.12.002. Epub 2020 Dec 30.

Abstract

Mammary gland ductal morphogenesis depends on the differentiation of mammary stem cells (MaSCs) into basal and luminal lineages. The AP-2γ transcription factor, encoded by Tfap2c, has a central role in mammary gland development but its effect in mammary lineages and specifically MaSCs is largely unknown. Here, we utilized an inducible, conditional knockout of Tfap2c to elucidate the role of AP-2γ in maintenance and differentiation of MaSCs. Loss of AP-2γ in the basal epithelium profoundly altered the transcriptomes and decreased the number of cells within several clusters of mammary epithelial cells, including adult MaSCs and luminal progenitors. AP-2γ regulated the expression of genes known to be required for mammary development, including Cebpb, Nfkbia, and Rspo1. As a result, AP-2γ-deficient mice exhibited repressed mammary gland ductal outgrowth and inhibition of regenerative capacity. The findings demonstrate that AP-2γ can regulate development of mammary gland structures potentially regulating maintenance and differentiation of multipotent MaSCs.

Keywords: AP-2γ; Tfap2c; development; mammary gland.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CCAAT-Enhancer-Binding Protein-beta / metabolism
  • Female
  • Gene Expression Regulation, Developmental
  • Mammary Glands, Animal / cytology
  • Mammary Glands, Animal / growth & development
  • Mammary Glands, Animal / metabolism
  • Mice
  • Mice, Knockout
  • Multipotent Stem Cells / cytology
  • Multipotent Stem Cells / metabolism*
  • NF-KappaB Inhibitor alpha / metabolism
  • Regeneration
  • Sequence Analysis, RNA
  • Single-Cell Analysis
  • Thrombospondins / metabolism
  • Transcription Factor AP-2 / deficiency
  • Transcription Factor AP-2 / genetics*

Substances

  • CCAAT-Enhancer-Binding Protein-beta
  • Cebpb protein, mouse
  • Nfkbia protein, mouse
  • RSPO1 protein, mouse
  • Thrombospondins
  • Transcription Factor AP-2
  • NF-KappaB Inhibitor alpha