Differential Network Analysis Reveals Regulatory Patterns in Neural Stem Cell Fate Decision

Deciphering regulatory patterns of neural stem cell (NSC) differentiation with multiple stages is essential to understand NSC differentiation mechanisms. Recent single-cell transcriptome datasets became available at individual differentiation. However, a systematic and integrative analysis of multiple datasets at multiple temporal stages of NSC differentiation is lacking. In this study, we propose a new method integrating prior information to construct three gene regulatory networks at pair-wise stages of transcriptome and apply this method to investigate five NSC differentiation paths on four different single-cell transcriptome datasets. By constructing gene regulatory networks for each path, we delineate their regulatory patterns via differential topology and network diffusion analyses. We find 12 common differentially expressed genes among the five NSC differentiation paths, with one common regulatory pattern (Gsk3b_App_Cdk5) shared by all paths. The identified regulatory pattern, partly supported by previous experimental evidence, is essential to all differentiation paths, but it plays a different role in each path when regulating other genes. Together, our integrative analysis provides both common and specific regulatory mechanisms for each of the five NSC differentiation paths.