Altered Epithelial-mesenchymal Plasticity as a Result of Ovol2 Deletion Minimally Impacts the Self-renewal of Adult Mammary Basal Epithelial Cells

J Mammary Gland Biol Neoplasia. 2021 Dec;26(4):377-386. doi: 10.1007/s10911-021-09508-0. Epub 2022 Jan 4.

Abstract

Stem-cell containing mammary basal epithelial cells exist in a quasi-mesenchymal transcriptional state characterized by simultaneous expression of typical epithelial genes and typical mesenchymal genes. Whether robust maintenance of such a transcriptional state is required for adult basal stem cells to fuel self-renewal and regeneration remains unclear. In this work, we utilized SMA-CreER to direct efficient basal cell-specific deletion of Ovol2, which encodes a transcription factor that inhibits epithelial-to-mesenchymal transition (EMT), in adult mammary gland. We identified a basal cell-intrinsic role of Ovol2 in promoting epithelial, and suppressing mesenchymal, molecular traits. Interestingly, Ovol2-deficient basal cells display minimal perturbations in their ability to support tissue homeostasis, colony formation, and transplant outgrowth. These findings underscore the ability of adult mammary basal cells to tolerate molecular perturbations associated with altered epithelia-mesenchymal plasticity without drastically compromising their self-renewal potential.

Keywords: Basal cell; Epithelial-mesenchymal plasticity; Epithelial-to-mesenchymal transition; Mammary gland; Ovol2; Stem cell.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Epithelial Cells* / metabolism
  • Epithelial-Mesenchymal Transition* / genetics
  • Gene Expression Regulation
  • Humans
  • Stem Cells / metabolism
  • Transcription Factors

Substances

  • Ovol2 protein, human
  • Transcription Factors