Hager C, Jehanno C, Bentires-Alj M
Department of Biomedicine, University of Basel, University Hospital Basel, Basel, Switzerland.
J Mammary Gland Biol Neoplasia. 2025 Jul 17;30(1):11. doi: 10.1007/s10911-025-09586-4.
Multipotency refers to the ability of a cell to differentiate into multiple, yet limited as opposed to pluripotency, number of cell types within a specific lineage or tissue. Studies using transgenic mouse models of the mammary gland have revealed a cellular hierarchy in which both luminal and basal lineages are replenished by unipotent progenitor cells. Hence, despite the existence of bipotent stem cells, normal mammary gland homeostasis is intimately linked with unipotency. However, recent literature revealed that under specific physiological or experimental conditions, lineage-restricted mammary cells can reacquire multipotency and undergo a lineage switch, challenging the traditional unidirectional model of cell differentiation. This reactivation of multipotency has been observed, for instance, in response to pregnancy, lineage ablation or oncogenic stimuli, indicating a certain level of plasticity that may have consequences in the context of tumorigenesis. Understanding the molecular mechanisms governing this phenomenon could provide valuable insights into mammary gland cellular hierarchy and breast cancer progression. Indeed, reactivation of multipotency is a result of developed cell plasticity, which can drive tumor heterogeneity, promote disease aggressiveness and hamper diagnosis. This review provides an overview of models that have inferred reactivation of multipotency, discusses the underlying molecular and cellular mechanisms and proposes future perspectives for research.
多能性是指细胞分化为多种细胞类型的能力，但与多能性相反，其分化的细胞类型数量在特定谱系或组织内是有限的。使用乳腺转基因小鼠模型的研究揭示了一种细胞层次结构，其中管腔谱系和基底谱系均由单能祖细胞补充。因此，尽管存在双能干细胞，但正常乳腺的稳态与单能性密切相关。然而，最近的文献表明，在特定的生理或实验条件下，谱系受限的乳腺细胞可以重新获得多能性并发生谱系转换，这对传统的细胞分化单向模型提出了挑战。例如，在妊娠、谱系消融或致癌刺激的情况下，已经观察到这种多能性的重新激活，这表明一定程度的可塑性可能在肿瘤发生的背景下产生影响。了解控制这一现象的分子机制可以为乳腺细胞层次结构和乳腺癌进展提供有价值的见解。事实上，多能性的重新激活是细胞可塑性发展的结果，它可以驱动肿瘤异质性、促进疾病侵袭性并阻碍诊断。本综述概述了推断多能性重新激活的模型，讨论了潜在的分子和细胞机制，并提出了未来的研究方向。
