Gene regulatory networks directing myeloid and lymphoid cell fates within the immune system.

Considerable progress is being achieved in the analysis of gene regulatory networks that direct cell fate decisions within the hematopoietic system. In addition to transcription factors that are pivotal for cell fate specification and commitment, recent evidence suggests the involvement of microRNAs. In this review we attempt to integrate these two types of regulatory components into circuits that dictate cell fate choices leading to the generation of innate as well as adaptive immune cells.

Transcription factor EBF restricts alternative lineage options and promotes B cell fate commitment independently of Pax5.

Alternative lineage restriction and B cell fate commitment require the transcription factor Pax5, but the function of early B cell factor (EBF) in these processes remains mostly unexplored. Here we show that in the absence of EBF, 'expandable' and clonal lymphoid progenitor cells retained considerable myeloid potential. Conversely, ectopic expression of EBF in multipotential progenitor cells directed B cell generation at the expense of myeloid cell fates.

Multilineage transcriptional priming and determination of alternate hematopoietic cell fates.

Hematopoietic stem cells and their progenitors exhibit multilineage patterns of gene expression. Molecular mechanisms underlying the generation and refinement of these patterns during cell fate determination remain unexplored because of the absence of suitable experimental systems. Using PU.

IRF-4,8 orchestrate the pre-B-to-B transition in lymphocyte development.

B-lymphocyte development involves sequential DNA rearrangements of immunoglobulin (Ig) heavy (mu) and light (kappa, lambda) chain loci and is dependent on transient expression of mu containing pre-antigen receptor complexes (pre-BCR). To date, genetic analysis has not identified transcription factors that coordinate the pre-B-to-B transition. We demonstrate that the related interferon regulatory factors IRF-4 (Pip) and IRF-8 (ICSBP) are required for Ig light but not heavy-chain gene rearrangement.

Cooperative and antagonistic interplay between PU.1 and GATA-2 in the specification of myeloid cell fates.

PU.1 and GATA transcription factors appear to antagonize each other's function in the development of distinct lineages of the hematopoietic system. In contrast, we demonstrate that PU.