Transcriptional networks regulating hematopoietic cell fate decisions

We provide a summary of the temporal cascade of transcriptional networks giving rise to the hematopoietic stem cell (HSC) and controlling differentiation of the erythroid lineage from it. We focus on the mechanisms by which cell fate decisions are made and comment on recent developments and additions to the networks.

A role for an SCL/LMO2 complex in HSC emergence, as well as in subsequent erythroid differentiation, has received support. Connections between the transcriptional networks and signaling molecules are being made but more work is needed in this area. Evidence that transcriptional cross-antagonistic switches underlie the choice between lineage pathways is increasing, and we highlight how the dynamics of earlier lineage decisions can influence later ones. Mathematical models are being built and reveal a surprising degree of power in these simple motifs to explain lineage choices.

New links in the transcriptional networks underlying cell-fate decisions are constantly emerging, and their incorporation into the evolving networks will make mathematical modeling more precise in its predictions of cell behavior, which can be tested experimentally.