Banerji CRS

Enver T

Miranda-Saavedra D

Severini S

Teschendorff AE

Widschwendter M

Zhou JX

Differentiation is a key cellular process in normal tissue development that is significantly altered in cancer. Although molecular signatures characterising pluripotency and multipotency exist, there is, as yet, no single quantitative mark of a cellular sample\u27s position in the global differentiation hierarchy. Here we adopt a systems view and consider the sample\u27s network entropy, a measure of signaling pathway promiscuity, computable from a sample\u27s genome-wide expression profile. We demonstrate that network entropy provides a quantitative, in-silico, readout of the average undifferentiated state of the profiled cells, recapitulating the known hierarchy of pluripotent, multipotent and differentiated cell types. Network entropy further exhibits dynamic changes in time course differentiation data, and in line with a sample\u27s differentiation stage. In disease, network entropy predicts a higher level of cellular plasticity in cancer stem cell populations compared to ordinary cancer cells. Importantly, network entropy also allows identification of key differentiation pathways. Our results are consistent with the view that pluripotency is a statistical property defined at the cellular population level, correlating with intra-sample heterogeneity, and driven by the degree of signaling promiscuity in cells. In summary, network entropy provides a quantitative measure of a cell\u27s undifferentiated state, defining its elevation in Waddington\u27s landscape

Newcastle University E-Prints

Cellular network entropy as the energy potential in Waddington’s differentiation landscape

https://eprint.ncl.ac.uk/file_store/production/195994/6CF080EA-D37C-49A6-8EF3-4A3257F43CB4.pdf

Cellular network entropy as the energy potential in Waddington’s differentiation landscape

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