Abstract
Single-cell transcriptomics offers a new vista on non-genetic tumor cell plasticity, a neglected aspect of cancer. The gene expression state of each cell is governed by the gene regulatory network which represents a high-dimensional non-linear dynamical system that generates multiple stable attractor states and undergoes destabilizing bifurcations, manifest as critical transitions. Modeling clonal cell population as statistical ensembles of the same dynamical system, a index IC is derived for detecting destabilization towards critical transitions in single-cell molecular profiles. Therapy-induced bifurcation explains why treatment backfires: a drug-treated cell is imposed the binary choice to either apoptose or become a cancer-stem cell.
Footnotes
Research supported by the NIH (NIGMS) and the Canadian NSERC and CIHR. S. Huang is at the Institute for Systems Biology, Seattle WA 98109, USA. Email: sui.huang{at}systemsbiology.org