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

oleh: Francesco Paolo Casale, Giorgio Giurato, Giovanni Nassa, Jonathan W Armond, Chris J Oates, Davide CorĂ¡, Andrea Gamba, Sach Mukherjee, Alessandro Weisz, Mario Nicodemi

Format: Article
Diterbitkan: Public Library of Science (PLoS) 2014-01-01

Deskripsi

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.