title: Single-cell states in the estrogen response of breast cancer cell lines.
abstract: Estrogen responsive breast cancer cell lines have been extensively studied to characterize transcriptional patterns in hormone-responsive tumors. Nevertheless, due to current technological limitations, genome-wide studies have typically been limited to population averaged data. Here we obtain, for the first time, a characterization at the single-cell level of the states and expression signatures of a hormone-starved MCF-7 cell system responding to estrogen. To do so, we employ a recently proposed model that allows for dissecting single-cell states from time-course microarray data. We show that within 32 hours following stimulation, MCF-7 cells traverse, most likely, six states, with a faster early response followed by a progressive deceleration. We also derive the genome-wide transcriptional profiles of such single-cell states and their functional characterization. Our results support a scenario where estrogen promotes cell cycle progression by controlling multiple, sequential regulatory steps, whose single-cell events are here identified.
authors.affiliation: European Molecular Biology Laboratory, European Bioinformatics Institute, Hinxton, Cambridge, United Kingdom.
authors.forename: Francesco Paolo
authors.initials: FP
authors.lastname: Casale
authors.affiliation: Department of Medicine and Surgery, Laboratory of Molecular Medicine and Genomics, University of Salerno, Baronissi, Salerno, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Giurato
authors.affiliation: Department of Medicine and Surgery, Laboratory of Molecular Medicine and Genomics, University of Salerno, Baronissi, Salerno, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Nassa
authors.affiliation: Centre for Complexity Science, University of Warwick, Coventry, United Kingdom.
authors.forename: Jonathan W
authors.initials: JW
authors.lastname: Armond
authors.affiliation: Centre for Complexity Science, University of Warwick, Coventry, United Kingdom.
authors.forename: Chris J
authors.initials: CJ
authors.lastname: Oates
authors.affiliation: Institute for Cancer Research and Treatment (IRCC), University of Turin School of Medicine, Candiolo, Turin, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Corá
authors.affiliation: Department of Applied Science and Technology, University of Turin, Istituto Nazionale di Fisica Nucleare (INFN), Human Genetics Foundation (HuGeF), Torino, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Gamba
authors.affiliation: Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Sach
authors.initials: S
authors.lastname: Mukherjee
authors.affiliation: Department of Medicine and Surgery, Laboratory of Molecular Medicine and Genomics, University of Salerno, Baronissi, Salerno, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Weisz
authors.affiliation: Department of Physics, University of Naples Federico II, CNR-Spin, Istituto Nazionale di Fisica Nucleare (INFN), Napoli, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Nicodemi
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism*; D002453:Cell Cycle / Q000235:genetics; D045744:Cell Line, Tumor; D004967:Estrogens / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D061986:MCF-7 Cells; D059467:Transcriptome / Q000235:genetics
chemical_list: D004967:Estrogens