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Foxp1 is indispensable for ductal morphogenesis and controls the exit of mammary stem cells from quiescence


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
2018-12-03
Developmental Cell
Journal Article
47
5
629-644 e8
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.
Cell Press
Stem Cells and Cancer; Bioinformatics; Molecular Genetics of Cancer
10.1016/j.devcel.2018.10.001
30523786
Refer to article for additional funding acknowledgements
Refer to copyright notice on published article.

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