biostudies-literatureTenno MRIKENPRESTOJapan Science and Technology AgencyCenter for Integrative Medical SciencesJapan Society for the Promotion of Science2933-2946https://www.ebi.ac.uk/biostudies/studies/S-EPMC5626404biostudies-literatureUnknown214(10)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 <i>Cbfb</i> 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 pThe Journal of experimental medicineCbfβ2 deficiency preserves Langerhans cell precursors by lack of selective TGFβ receptor signaling.PMC562640414F04214JPMJPR15F3JP 23790552JP 19390118Taniuchi IGinhoux FKoseki KMuroi SImanishi TShiroguchi KKryukov KKawakami ETenno MfalseCbfβ2 deficiency preserves Langerhans cell precursors by lack of selective TGFβ receptor signaling.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 <i>Cbfb</i> 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 p2017-01-01T00:00:00Z2017 Oct2026-04-29T08:49:12.572Z2019-06-06T18:12:31ZS-EPMC56264042881456710.1084/jem.20170729