Models of breast morphogenesis based on localization of stem cells in the developing mammary lobule.
Bottom Line: 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.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 iparous versus parous women and that of BRCA1/2 mutation carriers versus non-carriers.
Affiliation: Research Oncology, King's College London School of Medicine, London SE1 9RT, UK. Electronic address: firstname.lastname@example.org.Show MeSH
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Mentions: Combinations of these fate choices generated eight different models for lobule growth that differed in rate of growth and differentiation, as well as in localization and representation of stem cells within the developing lobule. In Figure 1, we show two examples of different outcomes in cell disposition within the lobule generated by different combinations of cell fate decision. All of the eight models are shown in Figure S1D. Two additional cell fates were also modeled, i.e., symmetric self-renewal of stem cells accompanied by asymmetric division of progeny (example shown in Figure S1E) and symmetric cell divisions of progenitor cells (example shown in Figure S1F). Other combinations including these cell fates are not presented here because the outcome cannot be distinguished from the models shown in Figure S1D, being different only in growth rate. For the simplicity of diagrams, only the luminal cell layer is shown. The myoepithelial layer is supposed to be generated from stem cells in the same direction as luminal cells. It is formed of fewer, longer cells with uniform morphology and marker expression.
Affiliation: Research Oncology, King's College London School of Medicine, London SE1 9RT, UK. Electronic address: email@example.com.