ArticleBreast cancer research : BCR2014
New insights into lineage restriction of mammary gland epithelium using parity-identified mammary epithelial cells.
Article in Breast cancer research : BCR, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 71 citations in OpenAlex.
- Looking in the Rear-View Mirror: How Lineage Tracing Experiments Redefined Cell Hierarchy in the Mammary Gland.Journal of mammary gland biology and neoplasia · 2026Review
- Defining breast epithelial cell types in the single-cell era.Developmental cell · 2025Review
- The molecular chronology of mammary epithelial cell fate switching.bioRxiv : the preprint server for biology · 2024Article
- Single-Cell Transcription Mapping of Murine and Human Mammary Organoids Responses to Female Hormones.Journal of mammary gland biology and neoplasia · 2024Article
- Validation of a new Custom Polyclonal Progesterone Receptor Antibody for Immunohistochemistry in the Female Mouse Brain.Journal of the Endocrine Society · 2023Article
- Innate Immune Program in Formation of Tumor-Initiating Cells from Cells-of-Origin of Breast, Prostate, and Ovarian Cancers.Cancers · 2023Review
- Effects of sustained hyperprolactinemia in late gestation on the mammary parenchymal tissue transcriptome of gilts.BMC genomics · 2023Article
- Loss of Brca1 and Trp53 in adult mouse mammary ductal epithelium results in development of hormone receptor-positive or hormone receptor-negative tumors, depending on inactivation of Rb family proteins.Breast cancer research : BCR · 2022Article
- Alveolar cells in the mammary gland: lineage commitment and cell death.The Biochemical journal · 2022Review
- Lineage Tracing Methods to Study Mammary Epithelial Hierarchies In Vivo.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Mammary gland development from a single cell 'omics view.Seminars in cell & developmental biology · 2021Review
- ΔN63 suppresses the ability of pregnancy-identified mammary epithelial cells (PIMECs) to drive HER2-positive breast cancer.Cell death & disease · 2021Article
- Got Milk? Identifying and Characterizing Lactation Defects in Genetically-Engineered Mouse Models.Journal of mammary gland biology and neoplasia · 2020Review
- Pregnancy reprograms the epigenome of mammary epithelial cells and blocks the development of premalignant lesions.Nature communications · 2020Article
- Integrating single-cell RNA-sequencing and functional assays to decipher mammary cell states and lineage hierarchies.NPJ breast cancer · 2020Review
- Breast Cancer During Pregnancy: A Marked Propensity to Triple-Negative Phenotype.Frontiers in oncology · 2020Review
- Remodeling of Murine Mammary Adipose Tissue during Pregnancy, Lactation, and Involution.Journal of mammary gland biology and neoplasia · 2019Review
- Overexpression of miR-489 derails mammary hierarchy structure and inhibits HER2/neu-induced tumorigenesis.Oncogene · 2019Article
- Stem Cells and Cellular Origins of Mammary Gland: Updates in Rationale, Controversies, and Cancer Relevance.Stem cells international · 2019Review
- Cellular Plasticity of Mammary Epithelial Cells Underlies Heterogeneity of Breast Cancer.Biomedicines · 2018Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionParity-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.
methodsWe 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.
resultsAfter 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.
conclusionsOur 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.
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