From genes to cells to tissues—modelling the haematopoietic system

Abstract

Haematopoiesis (or blood formation) in general and haematopoietic stem cells more specifically represent some of the best studied mammalian developmental systems. Sophisticated purification protocols coupled with powerful biological assays permit functional analysis of highly purified cell populations both in vitro and in vivo. However, despite several decades of intensive research, the sheer complexity of the haematopoietic system means that many important questions remain unanswered or even unanswerable with current experimental tools. Scientists have therefore increasingly turned to modelling to tackle complexity at multiple levels ranging from networks of genes to the behaviour of cells and tissues. Early modelling attempts of gene regulatory networks have focused on core regulatory circuits but have more recently been extended to genome-wide datasets such as expression profiling and ChIP-sequencing data. Modelling of haematopoietic cells and tissues has provided insight into the importance of phenotypic heterogeneity for the differentiation of normal progenitor cells as well as a greater understanding of treatment response for particular pathologies such as chronic myeloid leukaemia. Here we will review recent progress in attempts to reconstruct segments of the haematopoietic system. A variety of modelling strategies will be covered from small-scale, protein-DNA or protein-protein interactions to large scale reconstructions. Also discussed will be examples of how stochastic modelling may be applied to multi cell systems such as those seen in normal and malignant haematopoiesis.