Foxp1 is indispensable for ductal morphogenesis and controls the exit of mammary stem cells from quiescence
Details
Publication Year 2018-12-03, Volume 47, Issue #5, Page 629-644 e8
Journal Title
Developmental Cell
Publication Type
Journal Article
Abstract
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 Tspan8(hi) 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.
Publisher
Cell Press
WEHI Research Division(s)
Molecular Genetics Of Cancer; Bioinformatics; Stem Cells And Cancer
PubMed ID
30523786
Rights Notice
Refer to copyright notice on published article.


Creation Date: 2018-12-18 03:25:57
Last Modified: 2018-12-18 04:19:00
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