Journal
STEM CELL RESEARCH
Volume 15, Issue 2, Pages 376-383Publisher
ELSEVIER
DOI: 10.1016/j.scr.2015.08.001
Keywords
Jak/Stat pathway; Mammary stem/progenitor cells; Differentiation; Morphogenesis
Funding
- Canadian Institutes of Health Research (CIHR) [CIHR MOP 115105]
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Tissue development/remodeling requires modulations in both cellular architecture and phenotype. Aberration in these processes leads to tumorigenesis. During the pregnancy/lactation cycle the mammary epithelial cells undergo complex morphological and phenotypic programs resulting in the acquisition of apical/basal (A/B) polarization and cellular maturation necessary for proper lactation. Still the hormonal regulations and cellular mechanisms controlling these events are not entirely elucidated. Here we show that prolactin (PRL)/Jak2 pathway in mammary epithelial cells uniquely signals to establish A/B polarity as determined by the apical localization of the tight junction protein zona occludens 1 (ZO-1) and the basal/lateral localization of E-cadherin, and the apical trafficking of lipid droplets. As well, our results indicate that this pathway regulates mammary stem cell hierarchy by inducing the differentiation of luminal progenitor (EpCAM(hi)/CD49f(hi)) cells to mature luminal (EpCAM(hi)/CD49f(low)) cells. Moreover, our data indicate that PRL/Jak2 coordinates both of these cellular events through limiting the mitogen activated protein kinase (Erk1/2) pathway. Together our findings define a novel unifying mechanism coupling mammary epithelial cell A/B polarization and terminal differentiation. (C) 2015 The Authors. Published by Elsevier B.V.
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