Dendritic cells (DCs) are can be broadly divided into conventional (cDC) and plasmacytoid (pDC) subsets. Despite the importance of this lineage diversity, its genetic basis is not fully understood. We found that conditional ablation of the Ets-family transcription factor PU.1 in DC-restricted progenitors led to increased pDC production at the expense of cDCs. PU.1 controlled many of the cardinal functions of DCs, such as antigen presentation by cDCs and type I interferon production by pDCs. Conditional ablation of PU.1 de-repressed the pDC transcriptional signature in cDCs. The combination of genome-wide mapping of PU.1 binding and gene expression analysis revealed a key role for PU.1 in maintaining cDC identity through the induction of the transcriptional regulator DC-SCRIPT. PU.1 activated DC-SCRIPT expression, which in turn promoted cDC formation, particularly of cDC1s, and repressed pDC development. Thus, cDC identity is regulated by a transcriptional node requiring PU.1 and DC-SCRIPT.

树突状细胞（DC）可以大致分为常规（cDC）和浆细胞样（pDC）子集。尽管这种谱系多样性的重要性，但其遗传基础尚未完全了解。我们发现在DC限制的祖细胞中有条件地消融Ets家族转录因子PU.1导致增加了pDC的产生，却以cDCs为代价。PU.1控制了DC的许多基本功能，例如cDC的抗原呈递和pDC的I型干扰素产生。PU.1的条件消融抑制了cDC中的pDC转录特征。PU.1结合的全基因组定位和基因表达分析的结合揭示了PU.1通过诱导转录调节剂DC-SCRIPT维持cDC身份的关键作用。PU.1激活的DC-SCRIPT表达式，反过来促进了cDC的形成，尤其是cDC1的形成，并抑制了pDC的发展。因此，cDC身份由需要PU.1和DC-SCRIPT的转录节点调控。