Foxp1 Is Indispensable for Ductal Morphogenesis and Controls the Exit of Mammary Stem Cells from Quiescence
Nai Yang Fu, Bhupinder Pal, Yunshun Chen, Felicity C Jackling, Michael Milevskiy, Francois Vaillant, Bianca D Capaldo, Fusheng Guo, Kevin H Liu, Anne C Rios, Nicholas Lim, Andrew J Kueh, David M Virshup, Marco J Herold, Haley O Tucker, Gordon K Smyth, Geoffrey J Lindeman, Jane E Visvader
DEVELOPMENTAL CELL | CELL PRESS | Published : 2018
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 ..View full abstract
Awarded by Australian National Health and Medical Research Council (NHMRC)
Awarded by NHMRC Fellowships
We thank A. Chen and P. Jamieson for expert assistance and M. Ritchie for discussions. We are grateful to the Animal, Genotyping, FACS, Imaging and Histology facilities at WEHI. This work was supported by the Australian National Health and Medical Research Council (NHMRC) grants #1016701, #1054618, #1100807, #1113133; NHMRC IRIISS; the Victorian state government through VCA funding and Operational Infrastructure Support; and the Australian Cancer Research Foundation. N.Y.F. and A.C.R. were supported by a National Breast Cancer Foundation/Cure Cancer Australia Fellowship; G.K.S., and G.J.L. by NHMRC Fellowships #1058892, #1078730; and J.E.V. by NHMRC Fellowships #1037230 and 1102742.