Adult mammary stem cells (MaSCs) drive postnatal organogenesis and remodeling in the mammary gland, and their longevity and potential have important implications for breast cancer. However, despite intense investigation the identity, location, and differentiation potential of MaSCs remain subject to deliberation. The application of genetic lineage-tracing models, combined with quantitative 3D imaging and biophysical methods, has provided new insights into the mammary epithelial hierarchy that challenge classical definitions of MaSC potency and behaviors. We review here recent advances – discussing fundamental unresolved properties of MaSC potency, dynamics, and plasticity – and point to evolving technologies that promise to shed new light on this intractable debate. Elucidation of the physiological mammary differentiation hierarchy is paramount to understanding the complex heterogeneous breast cancer landscape.

成人乳腺干细胞 (MaSC) 驱动乳腺的出生后器官发生和重塑，它们的寿命和潜力对乳腺癌具有重要意义。然而，尽管进行了深入调查，但 MaSC 的身份、位置和分化潜力仍有待审议。遗传谱系追踪模型的应用，结合定量 3D 成像和生物物理方法，为挑战 MaSC 效力和行为的经典定义的乳腺上皮层次结构提供了新的见解。我们在这里回顾最近的进展——讨论 MaSC 效力、动力学和可塑性的基本未解决特性——并指出不断发展的技术，这些技术有望为这一棘手的争论提供新的思路。