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Title: Heterogeneity of Human Breast Stem and Progenitor Cells as Revealed by Transcriptional Profiling.

Authors: Colacino, Justin A; Azizi, Ebrahim; Brooks, Michael D; Harouaka, Ramdane; Fouladdel, Shamileh; McDermott, Sean P; Lee, Michael; Hill, David; Madden, Julie; Boerner, Julie; Cote, Michele L; Sartor, Maureen A; Rozek, Laura S; Wicha, Max S

Published In Stem Cell Reports, (2018 05 08)

Abstract: During development, the mammary gland undergoes extensive remodeling driven by stem cells. Breast cancers are also hierarchically organized and driven by cancer stem cells characterized by CD44+CD24low/- or aldehyde dehydrogenase (ALDH) expression. These markers identify mesenchymal and epithelial populations both capable of tumor initiation. Less is known about these populations in non-cancerous mammary glands. From RNA sequencing, ALDH+ and ALDH-CD44+CD24- human mammary cells have epithelial-like and mesenchymal-like characteristics, respectively, with some co-expressing ALDH+ and CD44+CD24- by flow cytometry. At the single-cell level, these cells have the greatest mammosphere-forming capacity and express high levels of stemness and epithelial-to-mesenchymal transition-associated genes including ID1, SOX2, TWIST1, and ZEB2. We further identify single ALDH+ cells with a hybrid epithelial/mesenchymal phenotype that express genes associated with aggressive triple-negative breast cancers. These results highlight single-cell analyses to characterize tissue heterogeneity, even in marker-enriched populations, and identify genes and pathways that define this heterogeneity.

PubMed ID: 29606612 Exiting the NIEHS site

MeSH Terms: Aldehyde Dehydrogenase/metabolism; Biomarkers/metabolism; Breast Neoplasms/genetics; Breast Neoplasms/pathology; Breast/cytology*; CD24 Antigen/metabolism; Cell Survival; Epithelium/metabolism; Female; Gene Expression Profiling*; Gene Expression Regulation, Neoplastic; Genes, Neoplasm; Humans; Hyaluronan Receptors/metabolism; Mesoderm/metabolism; Phenotype; Stem Cells/metabolism*; Transcriptome/genetics

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