title: Identification of Distinct Breast Cancer Stem Cell Populations Based on Single-Cell Analyses of Functionally Enriched Stem and Progenitor Pools.
abstract: The identification of breast cancer cell subpopulations featuring truly malignant stem cell qualities is a challenge due to the complexity of the disease and lack of general markers. By combining extensive single-cell gene expression profiling with three functional strategies for cancer stem cell enrichment including anchorage-independent culture, hypoxia, and analyses of low-proliferative, label-retaining cells derived from mammospheres, we identified distinct stem cell clusters in breast cancer. Estrogen receptor (ER)α+ tumors featured a clear hierarchical organization with switch-like and gradual transitions between different clusters, illustrating how breast cancer cells transfer between discrete differentiation states in a sequential manner. ERα- breast cancer showed less prominent clustering but shared a quiescent cancer stem cell pool with ERα+ cancer. The cellular organization model was supported by single-cell data from primary tumors. The findings allow us to understand the organization of breast cancers at the single-cell level, thereby permitting better identification and targeting of cancer stem cells.
authors.affiliation: Department of Pathology, Institute of Biomedicine, Sahlgrenska Cancer Center, Sahlgrenska Academy, University of Gothenburg, 40530 Gothenburg, Sweden.
authors.forename: Nina
authors.initials: N
authors.lastname: Akrap
authors.affiliation: Department of Pathology, Institute of Biomedicine, Sahlgrenska Cancer Center, Sahlgrenska Academy, University of Gothenburg, 40530 Gothenburg, Sweden.
authors.forename: Daniel
authors.initials: D
authors.lastname: Andersson
authors.affiliation: Department of Pathology, Institute of Biomedicine, Sahlgrenska Cancer Center, Sahlgrenska Academy, University of Gothenburg, 40530 Gothenburg, Sweden.
authors.forename: Eva
authors.initials: E
authors.lastname: Bom
authors.affiliation: Department of Pathology, Institute of Biomedicine, Sahlgrenska Cancer Center, Sahlgrenska Academy, University of Gothenburg, 40530 Gothenburg, Sweden.
authors.forename: Pernilla
authors.initials: P
authors.lastname: Gregersson
authors.affiliation: Department of Pathology, Institute of Biomedicine, Sahlgrenska Cancer Center, Sahlgrenska Academy, University of Gothenburg, 40530 Gothenburg, Sweden. Electronic address: anders.stahlberg@gu.se.
authors.forename: Anders
authors.initials: A
authors.lastname: Ståhlberg
authors.affiliation: Department of Pathology, Institute of Biomedicine, Sahlgrenska Cancer Center, Sahlgrenska Academy, University of Gothenburg, 40530 Gothenburg, Sweden. Electronic address: goran.landberg@gu.se.
authors.forename: Göran
authors.initials: G
authors.lastname: Landberg
mesh_terms: D023102:Anoikis / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation / Q000235:genetics; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D061986:MCF-7 Cells; D018613:Microscopy, Confocal; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D010641:Phenotype; D025341:Principal Component Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D059010:Single-Cell Analysis / Q000379:methods*; D055153:Stem Cell Niche / Q000235:genetics*
chemical_list: C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha