  Cellular reprogramming, the conversion of one cell type to another, has
fundamentally transformed our conception of cell types. Cellular reprogramming
induces global changes in gene expression involving hundreds of transcription
factors and thousands of genes and understanding how cells globally alter their
gene expression profile during reprogramming is an open problem. Here we
reanalyze time-series data on cellular reprogramming from differentiated cell
types to induced pluripotent stem cells (iPSCs) and show that gene expression
dynamics during reprogramming follow a simple one-dimensional reaction
coordinate. This reaction coordinate is independent of both the time it takes
to reach the iPSC state as well as the details of experimental protocol used.
Using Monte-Carlo simulations, we show that such a reaction coordinate emerges
naturally from epigenetic landscape models of cell identity where cellular
reprogramming is viewed as a "barrier-crossing" between the starting and ending
cell fates. The model also provides gene-level insight into reprogramming
dynamics and resolves a debate in the stem cell field about the different
phases of reprogramming dynamics. Overall, our analysis and model suggest that
gene expression dynamics during reprogramming follow a canonical trajectory
consistent with the idea of an "optimal path" in gene expression space for
reprogramming.
