Unmasking Stem Cell Dynamics in Mammary Branching Morphogenesis

Scheele et al. (2017) established that mammary stem cells (MaSCs) within terminal end buds (TEBs) drive post-pubertal mammary gland branching morphogenesis through dynamic positional regulation and cell mixing. Using lineage tracing and theoretical modeling, they found that nearly all duct branching results from TEB bifurcation, with MaSCs in the TEB contributing to duct elongation. Each TEB harbored approximately 260 MaSCs, which were unipotent, giving rise to either luminal or basal cells. The study also revealed significant intra-TEB cell migration, suggesting that MaSCs act as an equipotent pool over time. Single-cell RNA sequencing showed heterogeneity in gene expression among MaSCs, indicating a spectrum of luminal and basal states rather than a single transcriptional signature. Future research should explore how TEB-associated MaSC behaviors are regulated by microenvironmental signals.