The differentiation of myeloid progenitors is effected by cascading waves of coordinated gene expression that remodel cellular physiology in a characteristic sequence [RNA-seq]

We utilized non-negative matrix factorization to identify behaviors, characteristic temporal patterns of gene expression, and to classify transcripts by behavior. Only 10 distinct behaviors are sufficient to recapitulate the expression of ~36,000 transcripts with high fidelity. Gene expression in most of the behaviors occurs in pulses of varying initiation times and durations.

This implies that information transfer during differentiation occurs in cascading waves of gene expression culminating in the permanent turning on of certain genes after ~80h. Each behavior is enriched in specific biological processes, so that physiological remodeling proceeds in a characteristic order---signal transduction, translation and mRNA processing, metabolism, and, ultimately, myeloid phenotypic processes. The sharp transition at 8h corresponds to the completion of transcriptional and translational remodeling and the initiation of metabolic remodeling; the one at 80h corresponds to the elicitation of myeloid phenotypes.

Our analysis shows that differentiation relies upon a series of transient, rapid, and complex gene regulatory events and highlights the importance of profiling it at a high temporal resolution.