{"title":"Reactivation of Multipotency in the Mammary Gland - a Ripple in the Pond and a Turn of the Tide.","authors":"C Hager, C Jehanno, M Bentires-Alj","doi":"10.1007/s10911-025-09586-4","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":16413,"journal":{"name":"Journal of Mammary Gland Biology and Neoplasia","volume":"30 1","pages":"11"},"PeriodicalIF":3.6000,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12271291/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Mammary Gland Biology and Neoplasia","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s10911-025-09586-4","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
引用次数: 0
Abstract
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.
期刊介绍:
Journal of Mammary Gland Biology and Neoplasia is the leading Journal in the field of mammary gland biology that provides researchers within and outside the field of mammary gland biology with an integrated source of information pertaining to the development, function, and pathology of the mammary gland and its function.
Commencing in 2015, the Journal will begin receiving and publishing a combination of reviews and original, peer-reviewed research. The Journal covers all topics related to the field of mammary gland biology, including mammary development, breast cancer biology, lactation, and milk composition and quality. The environmental, endocrine, nutritional, and molecular factors regulating these processes is covered, including from a comparative biology perspective.