Supplementary Figure 8: Scheme summarizing the contribution of Lgr6⁺ cells to postnatal mammary gland development, pregnancy, and luminal mammary tumours.

(a) During postnatal development, two populations of Lgr6⁺ mammary epithelial progenitor cells (basal and luminal) contribute to ductal morphogenesis. In adult virgin females, however, Lgr6 + cells do not actively add to tissue homeostasis and their number decreases over time. Their clonal potential is reactivated by pregnancy (and stimulation with ovarian hormones) and they contribute to the alveolar network over multiple pregnancies. (b) Lgr6⁺ progenitors can function as potent cells of origin of luminal mammary tumours Transformation of Lgr6⁺ progenitor cells with two different oncogenic combinations (loss of p53 and Brca1, or activation of mutant K-Ras^G12D and loss of Fbxw7, respectively) resulted in the formation of exclusively luminal mammary tumours, appearing with high penetrance. (c) Lgr6⁺ cells contribute to luminal, but not basal mammary tumours. Lineage tracing showed that luminal Lgr6⁺ progenitors contribute to MMTV-PyMT-induced tumours. In contrast, neither basal nor luminal Lgr6-expressing cells were traced in chemically induced, basaloid DMBA/MPA tumours.