Global genetic regulatory networks controlling hematopoietic cell fates

Abstract

The gene expression profile of a cell is a consequence of transcription factor activities, which, in turn, are controlled by extra-cellular signals. The relationships between all these regulators constitute a genetic regulatory network, which can be used to predict the behavior of the cell in changing environments. We outline the progress being made to identify Genetic Regulatory Networks for hematopoiesis, using gene-by-gene approaches or emerging genomic technologies. The construction of genetic regulatory networks for single and multicellular organisms has inspired the building of genetic regulatory networks for erythropoiesis and B-cell differentiation. genetic regulatory networks are 'scale-free', whereby some genes have many connections while others have very few. The well connected genes, or hubs, correspond to master regulators of the networks, acting to integrate signals and control the sequential passage of the cells through the differentiation process. Lineage decisions are governed by cross-antagonism between two hubs. Large datasets from genome-wide analyses support the concept of multilineage priming and will increasingly refine the network topologies. As the underlying genetic regulatory networks for hematopoiesis continue to emerge, the program for lineage choice and differentiation will be revealed. More large-scale datasets identifying network components are needed alongside continued gene-by-gene analyses.