Genetic manipulation of individual somatic mammary cells in vivo reveals a master role of STAT5a in inducing alveolar fate commitment and lactogenesis even in the absence of ovarian hormones.
Assessing the molecular control of development and cell fate in individual cells in the intact mammary epithelium has not been possible to date. By exploiting an intraductal retrovirus (RCAS)-mediated gene delivery method to introduce a marker gene, we found that ductal epithelial cells are turned over with a half time of approximately 1month in adult virgin mice. However, following RCAS-mediated introduction of a constitutively activated STAT5a (caSTAT5a), caSTAT5a-activated ductal epithelial cells expand and replace other cells in the epithelium, eventually forming a mammary gland resembling that in a late pregnant mouse, suggesting that STAT5a activation alone is sufficient to mediate pregnancy-induced mammary cell expansion, alveolar cell fate commitment, and lactogenesis. Furthermore, such caSTAT5a-induced alveolar differentiation does not require ovarian functions, although caSTAT5a-induced cell proliferation is partly reduced in ovariectomized mice. In conclusion, in this first report of studying the developmental role of a gene in a few cells in a normally developed virgin mammary ductal tree, STAT5a activation causes alveolar fate commitment and lactogenesis, and with the help of ovarian hormones, drives alveolar expansion.
Dong
Jie
J
Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA.
Tong
Tammy
T
Reynado
Amanda M
AM
Rosen
Jeffrey M
JM
Huang
Shixia
S
Li
Yi
Y
D000818:Animals; D049109:Cell Proliferation; D002645:Chickens; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D008321:Mammary Glands, Animal / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D010053:Ovary / Q000378:metabolism*; D050799:STAT5 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
D050799:STAT5 Transcription Factor