Computational Modeling in Hematopoiesis

Abstract

Hematopoiesis is the process of blood cell generation from somatic stem cells. In this work, we apply a top-down view on regulatory networks in hematopoietic differentiation. From a literature-based large-scale model we extract a core set of known regulatory interactions responsible for the myeloid lineage decision. Boolean modeling of this central network reveals its ability to give rise to the four myeloid blood cell types. We develop a quantitative model for the mutually inhibitory interaction between the two lineage decision factors PU.1 and GATA-1. The cosuppressor PU.1 is proposed to be of major importance for the balancing of this interaction. Finally, an analysis pipeline for the experimental quantification of single-cell time-resoluted PU.1 protein expression is presented. Preliminary results from this dataset promise in-depth understanding of the lineage decision process in differentiating hematopoietic cells.