Dachshund Depletion Disrupts Mammary Gland Development and Diverts the Composition of the Mammary Gland Progenitor Pool

Publication date: Available online 13 December 2018Source: Stem Cell ReportsAuthor(s): Xuanmao Jiao, Zhiping Li, Min Wang, Sanjay Katiyar, Gabriele Di Sante, Mehdi Farshchian, Andrew P. South, Cinzia Cocola, Daniele Colombo, Rolland Reinbold, Ileana Zucchi, Kongming Wu, Ira Tabas, Benjamin T. Spike, Richard G. PestellSummaryDACH1 abundance is reduced in human malignancies, including breast cancer. Herein DACH1 was detected among multipotent fetal mammary stem cells in the embryo, among mixed lineage precursors, and in adult basal cells and (ERα+) luminal progenitors. Dach1 gene deletion at 6 weeks in transgenic mice reduced ductal branching, reduced the proportion of mammary basal cells (Lin− CD24med CD29high) and reduced abundance of basal cytokeratin 5, whereas DACH1 overexpression induced ductal branching, increased Gata3 and Notch1, and expanded mammosphere formation in LA-7 breast cells. Mammary gland-transforming growth factor β (TGF-β) activity, known to reduce ductal branching and to reduce the basal cell population, increased upon Dach1 deletion, associated with increased SMAD phosphorylation. Association of the scaffold protein Smad anchor for receptor activation with Smad2/3, which facilitates TGF-β activation, was reduced by endogenous DACH1. DACH1 increases basal cells, enhances ductal formation and restrains TGF-β activity in vivo.
Source: Stem Cell Reports - Category: Stem Cells Source Type: research