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Type: Journal article
Title: New insights into lineage restriction of mammary gland epithelium using parity-identified mammary epithelial cells
Author: Chang, T.
Kunasegaran, K.
Tarulli, G.
De Silva, D.
Voorhoeve, P.
Pietersen, A.
Citation: Breast Cancer Research, 2014; 16(1):R1-1-R1-16
Publisher: BioMed Central
Issue Date: 2014
ISSN: 1465-5411
Statement of
Ted H-T Chang, Kamini Kunasegaran, Gerard A Tarulli, Duvini De Silva, P Mathijs Voorhoeve, and Alexandra M Pietersen
Abstract: INTRODUCTION: Parity-identified mammary epithelial cells (PI-MECs) are an interesting cellular subset because they survive involution and are a presumptive target for transformation by human epidermal growth factor receptor 2 (HER2)/neu in mammary tumors. Depending on the type of assay, PI-MECs have been designated lobule-restricted progenitors or multipotent stem/progenitor cells. PI-MECs were reported to be part of the basal population of mammary epithelium based on flow cytometry. We investigated the cellular identity and lineage potential of PI-MECs in intact mammary glands. METHODS: We performed a quantitative and qualitative analysis of the contribution of PI-MECs to mammary epithelial cell lineages in pregnant and involuted mammary glands by immunohistochemistry, fluorescence-activated cells sorting (FACS), and quantitative polymerase chain reaction. PI-MECs were labeled by the activation of Whey Acidic Protein (WAP)-Cre during pregnancy that results in permanent expression of yellow fluorescent protein. RESULTS: After involution, PI-MECs are present exclusively in the luminal layer of mammary ducts. During pregnancy, PI-MECs contribute to the luminal layer but not the basal layer of alveolar lobules. Strikingly, whereas all luminal estrogen receptor (ER)-negative cells in an alveolus can be derived from PI-MECs, the alveolar ER-positive cells are unlabeled and reminiscent of Notch2-traced L cells. Notably, we observed a significant population of unlabeled alveolar progenitors that resemble PI-MECs based on transcriptional and histological analysis. CONCLUSIONS: Our demonstration that PI-MECs are luminal cells underscores that not only basal cells display multi-lineage potential in transplantation assays. However, the lineage potential of PI-MECs in unperturbed mammary glands is remarkably restricted to luminal ER-negative cells of the secretory alveolar lineage. The identification of an unlabeled but functionally similar population of luminal alveolar progenitor cells raises the question of whether PI-MECs are a unique population or the result of stochastic labeling. Interestingly, even when all luminal ER-negative cells of an alveolus are PI-MEC-derived, the basal cells and hormone-sensing cells are derived from a different source, indicating that cooperative outgrowth of cells from different lineages is common in alveologenesis.
Keywords: Mammary Glands, Animal; Epithelial Cells; Multipotent Stem Cells; Animals; Mice, Transgenic; Mice; Bacterial Proteins; Milk Proteins; Caseins; DNA-Binding Proteins; Luminescent Proteins; Integrin alpha6; Receptors, Estrogen; Transcription Factors; Flow Cytometry; Parity; Cell Differentiation; Cell Lineage; Pregnancy; Female; Antigens, CD24
Rights: © 2014 Chang et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated.
RMID: 0030031686
DOI: 10.1186/bcr3593
Appears in Collections:Medicine publications

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