C/EBPΑ is required for development of dendritic cell progenitors

Dendritic cells (DCs) are master regulators of the immune system, but molecular regulation of early DC differentiation has been poorly understood. Here, we report that the transcription factor C/EBPa coordinates the development of progenitor cells required for production of multiple categories of DCs. C/EBPa was needed for differentiation from stem/progenitor cells to common DC progenitors (CDPs), but not for transition of CDP to mature DCs. C/EBPa deletion in mature DCs did not affect their numbers or function, suggesting that this transcription factor is not needed for maintenance of DCs in lymphoid tissues. ChIP-seq and microarrays were used to identify candidate genes regulated by C/EBPa and required for DC formation. Genes previously shown to be critical for DC formation were bound by C/EBPa, and their expression was decreased in the earliest hematopoietic compartments in the absence of C/EBPa. These data indicate that C/EBPa is important for the earliest stages of steady-state DC differentiation.