The mouse Langerhans cell (LC) network is established through the differentiation of embryonic LC precursors. BMP7 and TGFβ1 initiate cellular signaling that is essential for inducing LC differentiation and preserving LCs in a quiescent state, respectively. Here we show that loss of Cbfβ2, one of two RNA splice variants of the Cbfb gene, results in long-term persistence of embryonic LC precursors after their developmental arrest at the transition into the EpCAM⁺ stage. This phenotype is caused by selective loss of BMP7-mediated signaling essential for LC differentiation, whereas TGFβR signaling is intact, maintaining cells in a quiescent state. Transgenic Cbfβ2 expression at the neonatal stage, but not at the adult stage, restored differentiation from Cbfβ2-deficient LC precursors. Loss of developmental potential in skin-residential precursor cells was accompanied by diminished BMP7–BMPR1A signaling. Collectively, our results reveal an essential requirement for the Cbfβ2 variant in LC differentiation and provide novel insight into how the establishment and homeostasis of the LC network is regulated.

小鼠朗格汉斯细胞（LC）网络是通过胚胎LC前体的分化而建立的。BMP7和TGFβ1分别启动细胞信号传导，这对于诱导LC分化和将LC保持在静止状态至关重要。在这里，我们显示Cbfb基因的两个RNA剪接变体之一Cbfβ2的丢失会导致胚胎LC前体在过渡到EpCAM ^+时的发育停滞后长期持久存在。阶段。这种表型是由选择性选择性丢失BMP7介导的LC分化必不可少的信号引起的，而TGFβR信号却是完整的，使细胞保持静止状态。新生阶段而非成年阶段的转基因Cbfβ2表达恢复了与缺乏Cbfβ2的LC前体的分化。BMP7–BMPR1A信号转导减少，导致皮肤驻留前体细胞发育潜能丧失。总的来说，我们的结果揭示了LC分化过程中Cbfβ2变体的基本要求，并为如何调节LC网络的建立和动态平衡提供了新颖的见解。