PLoS ONE (Jan 2014)

Single-cell states in the estrogen response of breast cancer cell lines.

  • Francesco Paolo Casale,
  • Giorgio Giurato,
  • Giovanni Nassa,
  • Jonathan W Armond,
  • Chris J Oates,
  • Davide Corá,
  • Andrea Gamba,
  • Sach Mukherjee,
  • Alessandro Weisz,
  • Mario Nicodemi

DOI
https://doi.org/10.1371/journal.pone.0088485
Journal volume & issue
Vol. 9, no. 2
p. e88485

Abstract

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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.