Models of Breast Morphogenesis Based on Localization of Stem Cells in the Developing Mammary Lobule
Models of Breast Morphogenesis Based on Localization of Stem Cells in the Developing Mammary Lobule
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DOI：
10.1016/j.stemcr.2015.02.013
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发表时间：
2015-04-14
影响因子：
5.9
通讯作者：
Dontu, Gabriela
中科院分区：
文献类型：
--
作者：
Honeth, Gabriella;Schiavinotto, Tommaso;Dontu, Gabriela
正常乳腺干细胞的特征对于了解它们在乳房发育和乳腺癌中的作用很重要。然而，这些细胞的身份是一个有争议的主题，它们在乳腺上皮中的定位尚不清楚。在这项研究中，我们使用了一种新的方法来分析乳腺小叶的形态发生，结合了一维理论模型和计算机生成的三维分形图。将这些模型的预测与组织切片中候选干细胞标记的免疫组织化学分析进行比较，我们定义了干细胞驻留在乳腺小叶中的不同区域。与更大、更成熟的小叶相比，干细胞在较小、发育较差的小叶中的表达增加，在未分娩妇女和经产妇女以及BRCA1/2突变携带者和非携带者的腺体中存在显著差异。
Characterization 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.