期刊
JOURNAL OF EXPERIMENTAL MEDICINE
卷 214, 期 10, 页码 2933-2946出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20170729
关键词
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资金
- Japan Society for the Promotion of Science KAKENHI [14F04214, JP 19390118, JP 23790552]
- RIKEN Center for Integrative Medical Sciences YCI program
- Japan Science and Technology Agency/PRESTO [JPMJPR15F3]
- Grants-in-Aid for Scientific Research [16KT0196, 17H05805, 14F04214] Funding Source: KAKEN
The mouse Langerhans cell (LC) network is established through the differentiation of embryonic LC precursors. BMP7 and TGF beta 1 initiate cellular signaling that is essential for inducing LC differentiation and preserving LCs in a quiescent state, respectively. Here we show that loss of Cbf beta 2, 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 TGF beta R signaling is intact, maintaining cells in a quiescent state. Transgenic Cbf beta 2 expression at the neonatal stage, but not at the adult stage, restored differentiation from Cbf beta 2-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 Cbf beta 2 variant in LC differentiation and provide novel insight into how the establishment and homeostasis of the LC network is regulated.
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