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

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

Format: Article
Diterbitkan: Elsevier 2018-05-01

Deskripsi

Summary: 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. : In this article, Colacino and colleagues use flow-cytometry-sorted populations and single-cell analyses to investigate human mammary stem cells. They discover unexpected phenotypic and functional heterogeneity at the single-cell level, including a subpopulation of ALDH+ stem cells with a hybrid epithelial/mesenchymal phenotype and triple-negative breast cancer-like gene expression pattern. Keywords: breast stem cell, single-cell RNA, epithelial, mesenchymal, hybrid, RNA-seq