Studying cell phenotype transition (CPT) is important for understanding of different biological processes like development, fibrosis, and cell migration. Fixed cell based single cell profiling and live cell imaging become powerful and indispensable tools for CPT studies. Recent advances of single cell techniques catalyzed quantitative studies on the dynamics of CPT emerging as a new field. Through analyzing single cell RNA sequencing data in the framework of transition path theory, we reconstructed reaction coordinates describing the transition progression in five CPT processes and inferred the gene regulation network (GRN) along the reaction coordinates of each CPT process. In all processes, we observed common pattern that the overall effective number and strength of regulation between different communities increase first and then decrease. The change accompanies with similar change of the GRN frustration, defined as overall conflict between the regulation received by genes and their expression states, and GRN heterogeneity. Our analyses reveal a general principle that during a cell phenotypic transition, intercommunity interactions increase to concertedly coordinate global gene expression reprogramming, and canalize to specific cell phenotype as Waddington visioned. Even though different CPTs mainly show concerted variation, some CPTs such as pancreatic endocrinogenesis may adopt a mixed strategy of concerted and sequential mechanisms.

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