Please use this identifier to cite or link to this item: https://doi.org/10.1186/bcr3593
Title: New insights into lineage restriction of mammary gland epithelium using parity-identified mammary epithelial cells
Authors: Chang, T.H.-T.
Kunasegaran, K.
Tarulli, G.A.
De Silva, D.
Voorhoeve, P.M. 
Pietersen, A.M.
Issue Date: 7-Jan-2014
Citation: Chang, T.H.-T., Kunasegaran, K., Tarulli, G.A., De Silva, D., Voorhoeve, P.M., Pietersen, A.M. (2014-01-07). New insights into lineage restriction of mammary gland epithelium using parity-identified mammary epithelial cells. Breast Cancer Research 16 (1) : -. ScholarBank@NUS Repository. https://doi.org/10.1186/bcr3593
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. © 2014 Chang et al.; licensee BioMed Central Ltd.
Source Title: Breast Cancer Research
URI: http://scholarbank.nus.edu.sg/handle/10635/110592
ISSN: 14655411
DOI: 10.1186/bcr3593
Appears in Collections:Staff Publications

Show full item record
Files in This Item:
There are no files associated with this item.

SCOPUSTM   
Citations

35
checked on Sep 11, 2019

WEB OF SCIENCETM
Citations

33
checked on Sep 11, 2019

Page view(s)

46
checked on Sep 6, 2019

Google ScholarTM

Check

Altmetric


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.