Reconstruction of dynamic regulatory networks reveals signaling-induced topology changes associated with germ layer specification.

ABSTRACT: Elucidating regulatory relationships between transcription factors (TFs) and target genes is fundamental to understanding how cells control their identity and behavior. Unfortunately, existing computational gene regulatory network (GRN) reconstruction methods are imprecise, computationally burdensome, and fail to reveal dynamic regulatory topologies. Here, we present Epoch, a reconstruction tool that uses single-cell transcriptomics to accurately infer dynamic networks. We apply Epoch to identify the dynamic networks underpinning directed differentiation of mouse embryonic stem cells (ESCs) guided by multiple signaling pathways, and we demonstrate that modulating these pathways drives topological changes that bias cell fate potential. We also find that Peg3 rewires the pluripotency network

SUBMITTER: Su EY 

PROVIDER: S-EPMC8828556 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature