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Models of breast morphogenesis based on localization of stem cells in the developing mammary lobule

Honeth, Gabriella LU ; Schiavinotto, Tommaso; Vaggi, Federico; Marlow, Rebecca; Kanno, Tokuwa; Shinomiya, Ireneusz; Lombardi, Sara; Buchupalli, Bharath; Graham, Rosalind and Gazinska, Patrycja, et al. (2015) In Stem Cell Reports 4(4). p.699-711
Abstract

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... (More)

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.

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@article{b00a844b-a740-480b-bf72-097041b2220b,
  abstract     = {<p>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.</p>},
  author       = {Honeth, Gabriella and Schiavinotto, Tommaso and Vaggi, Federico and Marlow, Rebecca and Kanno, Tokuwa and Shinomiya, Ireneusz and Lombardi, Sara and Buchupalli, Bharath and Graham, Rosalind and Gazinska, Patrycja and Ramalingam, Vernie and Burchell, Joy and Purushotham, Anand D and Pinder, Sarah E and Csikasz-Nagy, Attila and Dontu, Gabriela},
  issn         = {2213-6711},
  keyword      = {Biomarkers,Cell Differentiation,Epithelium,Female,Humans,Mammary Glands, Human,Models, Biological,Organogenesis,Stem Cells,Tissue Culture Techniques,Journal Article,Research Support, Non-U.S. Gov't},
  language     = {eng},
  month        = {04},
  number       = {4},
  pages        = {699--711},
  publisher    = {Cell Press},
  series       = {Stem Cell Reports},
  title        = {Models of breast morphogenesis based on localization of stem cells in the developing mammary lobule},
  url          = {http://dx.doi.org/10.1016/j.stemcr.2015.02.013},
  volume       = {4},
  year         = {2015},
}