Abstract
Organogenesis is a biological process of cell fate transition. Underlying this process are complex changes in the transcriptome. Although these changes have been described extensively in terms of individual genes or pathways, a mcroscale description of gene regulatory network dynamics is lacking. Leveraging time-series data from single-cell transcriptome profiling of developing mouse embryos, we present a novel analytic framework to aggregate dynamic gene expressions across the transcriptome into state changes in 14 core biological processes, and to construct an ordinary differential equation-based mathematical model of the macroscale network capturing its feedback structure. We determine the polarity and magnitude of direct pairwise causal relationships between biological processes and identify higher-order feedback interactions that dominate system behaviour. Despite heterogenous expressions at the gene level, we find that the transcriptome at the macroscale level has a feedback structure that is intrinsically stable and robust. We show the pivotal role of signaling in driving systemic changes and uncover the importance of homeostatic process and establishment of localization in regulating network dynamics. Localized regulatory structures represent domain-specific regulations that are essential to cell fate transition, especially lipid metabolic process. Altogether, this study not only provides a holistic picture of macroscale transcriptome dynamics during mouse organogenesis, but also offers insight into key aspects of information flow in the transcriptome that control cell fate transition.
Competing Interest Statement
The authors have declared no competing interest.