In vitro propagation and transcriptional profiling of human mammary stem/progenitor cells.

By G. Dontu, W. Abdallah, J. Foley, Kyle W. Jackson, M. Clarke, M. Kawamura, M. Wicha. Genes & Development, 2003

2,424 citations recorded by the source corpus.

Although the existence of mammary stem cells has been suggested by serial transplantation studies in mice, their identification has been hindered by the lack of specific surface markers, and by the absence of suitable in vitro assays for testing stem cell properties: self-renewal and ability to generate differentiated progeny. We have developed an in vitro cultivation system that allows for propagation of human mammary epithelial cells (HMECs) in an undifferentiated state, based on their ability to proliferate in suspension, as nonadherent mammospheres. We demonstrate that nonadherent mammospheres are enriched in early progenitor/stem cells and able to differentiate along all three mammary epithelial lineages and to clonally generate complex functional structures in reconstituted 3D culture systems. Gene expression analysis of cells isolated from nonadherent mammospheres revealed overlapping genetic programs with other stem and progenitor cells and identified new markers that may be useful in the identification of mammary stem cells. The isolation and characterization of these stem cells should help elucidate the molecular pathways that govern normal mammary development and carcinogenesis.

Subfields: Genetics, Oncology

View Paper: https://www.semanticscholar.org/paper/c2f09e4a0ca3ff243ccf3257b9d29af0bbba87a9

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Citations in the corpus

The Hippo transducer TAZ confers cancer stem cell-related traits on breast cancer cells. (2011, methodology): “…CD24low cells are endowed with better longterm self-renewal capacity as measured by mammosphere assays (Figure 3C); (3) CD44high/CD24low cells include the so-called ‘‘side population (SP)’’ (Figure S3D), which is defined by its ability to exclude the Hoechst vital dye (Dontu et al., 2003).”
Biological and molecular heterogeneity of breast cancers correlates with their cancer stem cell content. (2010, methodology): “We also used 3D Matrigel cultures, in which hNMSCs can generate mammary gland organotypic outgrowths (Dontu et al., 2003).”
Distinct stem cells contribute to mammary gland development and maintenance (2011, positive): “Culturing MECs as non-adherent cells, called mammospheres, allowed renewal and differentiation of cells with unipotent and bipotent differentiation potentia”
Human breast cancer cell lines contain stem-like cells that self-renew, give rise to phenotypically diverse progeny and survive chemotherapy (2008, background): “Sphere formation mimics tissue regeneration and correlates with tumorigenicity Suspension sphere cultures have been used to enrich for and characterize stem/progenitor cells from primary breast and glioblastomic tissues [24,27, 28 ].”
Transient Low Doses of DNA Demethylating Agents Exert Durable Anti-tumor Effects on Hematological and Epithelial Tumor Cells (2012, background): “…for self-renewal capacity and stem-like cell activity (Figure 4A) (McDermott andWicha, 2010; Korkaya et al., 2009; Charafe-Jauffret et al., 2009; Dontu et al., 2003; Ginestier et al., 2007; (C) gH2AX foci formation in CD34+ and CD34 Kasumi-1 cells after 72 hr DAC trea calculated as fold change…”
Inducible formation of breast cancer stem cells and their dynamic equilibrium with non-stem cancer cells via IL6 secretion (2011, methodology): “For serial passaging, 6-d-old mammospheres were harvested by using a 70-μm cell strainer, whereupon they were dissociated to single cells with trypsin (37), and then regrown in suspension for 6 d.”
A tumorigenic subpopulation with stem cell properties in melanomas. (2005, background): “normal and tumor tissues were isolated (3, 5, 40, 41), suggesting”
Spherical Cancer Models in Tumor Biology (2015, background): “…(from patient tumor-derived xenografts) [176] Neurospheres (normal and malignant brain) [35,36] Mammospheres (normal and malignant breast) [37,38] Colon cancer spheres (colon cancer) [39] Tissue-derived tumor spheres Colospheres [15,20] Cancer tissue – originated spheroids [16] Spheroids…”
Stochastic state transitions give rise to phenotypic equilibrium in populations of cancer cells. (2011, positive): “, 2005) todeterminewhether theexpression levels of genes previously reported to be associated with stem, basal, and luminal differentiationwere specifically enriched in the relevant sorted subpopulations (Assou et al., 2007; Blackman et al., 2005; Böcker et al., 2002; Brambrink et al., 2008; Bussola”
The tumor suppressor p53 regulates polarity of self-renewing divisions in mammary stem cells. (2009, methodology): “…CH-1015 Lausanne, Switzerland 4Dipartimento di Medicina, Chirurgia ed Odontoiatria, Universita’ degli Studi di Milano, Via A. di Rudini’ 8, 20122 Milan, Italy 5These authors contributed equally to this work *Correspondence: pierpaolo.difiore@ifom-ieo-campus.it (P.P.D.F.),…”