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.
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