Models of Breast Morphogenesis Based on Localization of Stem Cells in the Developing Mammary Lobule

• The morphology of mammary lobules can be computer modeled
• Stem cells identified by multiple markers have distinct localization in the breast
• Immature mammary lobules contain a higher percentage of stem cells
• This enrichment is higher in the breast of nulliparous women and BRCA1/2 carriers

SummaryCharacterization of normal breast stem cells is important for understanding their role in breast development and in breast cancer. However, the identity of these cells is a subject of controversy and their localization in the breast epithelium is not known. In this study, we utilized a novel approach to analyze the morphogenesis of mammary lobules, by combining one-dimensional theoretical models and computer-generated 3D fractals. Comparing predictions of these models with immunohistochemical analysis of tissue sections for candidate stem cell markers, we defined distinct areas where stem cells reside in the mammary lobule. An increased representation of stem cells was found in smaller, less developed lobules compared to larger, more mature lobules, with marked differences in the gland of nulliparous versus parous women and that of BRCA1/2 mutation carriers versus non-carriers.

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