RESUMEN
Myeloid cell heterogeneity remains poorly studied in breast cancer, and particularly in premalignancy. Here, we used single cell RNA sequencing to characterize macrophage diversity in mouse pre-invasive lesions as compared to lesions undergoing localized invasion. Several subpopulations of macrophages with transcriptionally distinct profiles were identified, two of which resembled macrophages in the steady state. While all subpopulations expressed tumor-promoting genes, many of the populations expressed pro-inflammatory genes, differing from reports in tumor-associated macrophages. Gene profiles of the myeloid cells were similar between early and late stages of premalignancy, although expansion of some subpopulations occurred. These results unravel macrophage heterogeneity in early progression and may provide insight into early intervention strategies that target macrophages.
RESUMEN
Mammary gland development is a complex and dynamic process that occurs mainly postnatally. Ductal elongation and branching morphogenesis are regulated by a plethora of factors, including cytokines, hormones, growth factors and the extracellular matrix. Gas6 is a secreted gamma-carboxylated protein that binds to a family of receptors tyrosine kinase receptors known as the TAMR family (Tyro3, Axl, Mer). Gas6 function in developmental processes has been shown in nervous, reproductive and immune systems. In this study, we found that Gas6 is highly expressed in virgin adult mammary glands but declines during pregnancy and lactation. Specifically, Gas6 is highly expressed in luminal and basal mammary epithelial cells during puberty and adulthood, while TAMR expression is low. Mammary whole mount analysis revealed that Gas6 germline deletion does not impact ductal elongation, branching morphogenesis or terminal end bud formation. Masson's trichrome staining showed that collagen deposition is similar in Gas6-/- mice as compared to wildtype mice. Gas6-/- mammary glands presented an organized luminal and myoepithelial bilayer of cells, and the proportion of mammary stem cells was unchanged in Gas6-/- mammary glands as compared to wildtype. Finally, proliferation of epithelial cells and macrophage number were similar in both groups. These studies suggest that Gas6 is not essential for pubertal mammary gland development in nulliparous mice.
