Foxp1 Is Indispensable for Ductal Morphogenesis and Controls the Exit of Mammary Stem Cells from Quiescence.

Published

Journal Article

Long-lived quiescent mammary stem cells (MaSCs) are presumed to coordinate the dramatic expansion of ductal epithelium that occurs through the different phases of postnatal development, but little is known about the molecular regulators that underpin their activation. We show that ablation of the transcription factor Foxp1 in the mammary gland profoundly impairs ductal morphogenesis, resulting in a rudimentary tree throughout life. Foxp1-deficient glands were highly enriched for quiescent Tspan8hi MaSCs, which failed to become activated even in competitive transplantation assays, thus highlighting a cell-intrinsic defect. Foxp1 deletion also resulted in aberrant expression of basal genes in luminal cells, inferring a role in cell-fate decisions. Notably, Foxp1 was uncovered as a direct repressor of Tspan8 in basal cells, and deletion of Tspan8 rescued the defects in ductal morphogenesis elicited by Foxp1 loss. Thus, a single transcriptional regulator Foxp1 can control the exit of MaSCs from dormancy to orchestrate differentiation and development.

Full Text

Duke Authors

Cited Authors

  • Fu, NY; Pal, B; Chen, Y; Jackling, FC; Milevskiy, M; Vaillant, F; Capaldo, BD; Guo, F; Liu, KH; Rios, AC; Lim, N; Kueh, AJ; Virshup, DM; Herold, MJ; Tucker, HO; Smyth, GK; Lindeman, GJ; Visvader, JE

Published Date

  • December 3, 2018

Published In

Volume / Issue

  • 47 / 5

Start / End Page

  • 629 - 644.e8

PubMed ID

  • 30523786

Pubmed Central ID

  • 30523786

Electronic International Standard Serial Number (EISSN)

  • 1878-1551

Digital Object Identifier (DOI)

  • 10.1016/j.devcel.2018.10.001

Language

  • eng

Conference Location

  • United States