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

Gabriella Honeth, Tommaso Schiavinotto, Federico Vaggi, Rebecca Marlow, Tokuwa Kanno, Ireneusz Shinomiya, Sara Lombardi, Bharath Buchupalli, Rosalind Graham, Patrycja Gazinska, Vernie Ramalingam, Joy Burchell, Anand D Purushotham, Sarah E Pinder, Attila Csikasz-Nagy, Gabriela Dontu

Research output: Contribution to journalArticlepeer-review

30 Citations (Scopus)
222 Downloads (Pure)

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 mature lobules, with marked differences in the gland of nulliparous versus parous women and that of BRCA1/2 mutation carriers versus non-carriers.

Original languageEnglish
Pages (from-to)699-711
Number of pages13
JournalStem Cell Reports
Volume4
Issue number4
DOIs
Publication statusPublished - 14 Apr 2015

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