Back to Search
Start Over
Foxp1 Is Indispensable for Ductal Morphogenesis and Controls the Exit of Mammary Stem Cells from Quiescence.
- Source :
-
Developmental cell [Dev Cell] 2018 Dec 03; Vol. 47 (5), pp. 629-644.e8. Date of Electronic Publication: 2018 Oct 25. - Publication Year :
- 2018
-
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 <superscript>hi</superscript> 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.<br /> (Copyright © 2018 Elsevier Inc. All rights reserved.)
- Subjects :
- 3T3 Cells
Adult Stem Cells cytology
Animals
Cells, Cultured
Female
Forkhead Transcription Factors genetics
HEK293 Cells
Humans
Mammary Glands, Human cytology
Mammary Glands, Human metabolism
Mice
Mice, Inbred C57BL
Repressor Proteins genetics
Tetraspanins genetics
Tetraspanins metabolism
Adult Stem Cells metabolism
Cell Differentiation
Forkhead Transcription Factors metabolism
Mammary Glands, Human growth & development
Morphogenesis
Repressor Proteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1878-1551
- Volume :
- 47
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Developmental cell
- Publication Type :
- Academic Journal
- Accession number :
- 30523786
- Full Text :
- https://doi.org/10.1016/j.devcel.2018.10.001