PU.1 is an essential regulator of hematopoiesis
PU.1 is required for all foetal lymphoid and myeloid lineages and embryonic viability. To investigate the function of PU.1 in adult hematopoiesis we have produced a conditional PU.1 knockout allele. This allele also introduces the GFP mRNA under the control of the endogenous regulatory elements to produce a PU.1 reporter. Analysis of PU.1-GFP mice has revealed that the levels of PU.1 in bone marrow progenitors corresponds to their developmental potential, with the down-regulation of PU.1 in multipotent myeloid progenitors representing the earliest event yet identified in the separation of the erythroid and myeloid pathways. We have also examined the consequence of PU.1 loss in adult hematopoiesis using conditional mutagenesis and demonstrated that PU.1 deficiency results greatly enhanced granulopoiesis and ultimately leukaemia. Currently we are characterising the function of PU.1 is specific cell types and at distinct developmental stages.
