PerspectiveSTEM CELLS

Macrophages stimulate mammary stem cells

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Science  29 Jun 2018:
Vol. 360, Issue 6396, pp. 1401-1402
DOI: 10.1126/science.aau1394

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The adult mammary gland is a bilayered branching epithelial structure consisting of an outer layer of basal cells and an inner layer of luminal cells. The neonatal structure expands rapidly during puberty and then undergoes cyclic growth in response to the changing hormonal stimuli (progesterone and estrogen) in each menstrual cycle (1). These dynamic responses of the mammary gland involve important interactions with various surrounding nonepithelial cells that constitute its “niche.” Circulating macrophages are important constituents of this niche although the mechanism through which they influence mammary cell proliferation has remained unclear. On page 1421 of this issue, Chakrabarti et al. (2) show that mouse mammary stem cells [cells with an ability to regenerate an entire mammary gland (3, 4)] are enriched within a subset of cells with a phenotype of basal layer cells and express the delta-like 1 (DLL1) NOTCH ligand, which allows them to interact with nearby NOTCH-expressing macrophages. This interaction triggers the production of multiple Wnt (Wingless-related integration site) ligands that, in turn, induce an expansion of the mammary stem cell population. This finding is important because it has implications for understanding how breast cancer may develop.