Identification of Biomarkers Controlling Cell Fate In Blood Cell Development

Abstract

A blood cell lineage consists of several consecutive developmental stages starting from the pluri- or multipotent stem cell to a state of terminal differentiation. Despite their importance for human biology, the regulatory pathways and gene networks that govern these differentiation processes are not yet fully understood. This is in part due to challenges associated with delineating the interactions between transcription factors (TFs) and their corresponding target genes. A possible step forward in this case is provided by the increasing amount of expression data, as a basis for linking differentiation stages and gene activities. Here, we present a novel hierarchical approach to identify characteristic expression peak patterns that global regulators excert along the differentiation path of cell lineages. Based on such simple patterns, we identified cell state-specific marker genes and extracted TFs that likely drive their differentiation. Integration of the mean expression values of stage-specific “key player” genes yielded a distinct peaking pattern for each lineage that was used to identify further genes in the dataset which behave similarly. Incorporating the set of TFs that regulate these genes led to a set of stage-specific regulators that control the biological process of cell fate. As proof of concept, we considered two expression datasets covering key differentiation events in blood cell formation of mice.