Data-driven modeling predicts gene regulatory network dynamics during the differentiation of multipotential hematopoietic progenitors.

ABSTRACT: Cellular differentiation during hematopoiesis is guided by gene regulatory networks (GRNs) comprising transcription factors (TFs) and the effectors of cytokine signaling. Based largely on analyses conducted at steady state, these GRNs are thought to be organized as a hierarchy of bistable switches, with antagonism between Gata1 and PU.1 driving red- and white-blood cell differentiation. Here, we utilize transient gene expression patterns to infer the genetic architecture-the type and strength of regulatory interconnections-and dynamics of a twelve-gene GRN including key TFs and cytokine receptors. We trained gene circuits, dynamical models that learn genetic architecture, on high temporal-resolution gene-expression data from the differentiation of an inducible cell line into erythrocytes a

SUBMITTER: Handzlik JE 

PROVIDER: S-EPMC8794271 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature