Lineage tracing of cells expressing the ciliary gene IFT140 during bone development
Lineage tracing of cells expressing the ciliary gene IFT140 during bone development
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骨骼发育过程中表达睫状基因 IFT140 的细胞谱系追踪
DOI：
10.1002/dvdy.266
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发表时间：
2020-12-05
影响因子：
2.5
通讯作者：
Sun, Yao
中科院分区：
文献类型：
--
作者：
Chen, Yubei;Fan, Qiqi;Sun, Yao
背景初级纤毛影响细胞功能和组织发育。纤毛信号传导由两种鞭毛内转运 (IFT) 蛋白复合物 IFT-A 和 IFT-B 介导。 IFT-A复合物负责逆行运输，IFT140是A复合物中的核心蛋白。 IFT140 突变会导致多种骨骼疾病。然而，IFT140在骨发育过程中的表达和作用仍不清楚。在本研究中，为了进一步探讨IFT140在成骨中的潜在作用，我们采用细胞谱系示踪和条件敲除的方法来分析IFT140阳性细胞在骨形成过程中的分布和功能。 R26R(tdTomato)小鼠中，IFT140阳性细胞主要定位于髓腔，随后迁移至小梁骨和皮质骨表面并分化。相比之下，IFT140阳性细胞的数量在成体阶段显着减少，并且这些细胞仅短暂位于骨髓腔中。在Osx-cre中； Ift140(flox/flox)小鼠，10周时前成骨细胞中IFT140的缺失导致骨小梁区骨质流失。结论结果显示IFT140阳性细胞主要参与早期骨形成。
Background Primary cilia influence cell function and tissue development. Ciliary signaling is mediated by two intraflagellar transport (IFT) protein complexes, IFT-A and IFT-B. The IFT-A complex is responsible for retrograde transport, and IFT140 is a core protein in the A complex. Mutations in IFT140 cause a variety of skeletal disorders. However, the expression and role of IFT140 during bone development remain unclear. In this study, to further explore the potential role of IFT140 in osteogenesis, we used cell lineage tracing and conditional knockout to analyze the distribution and function of IFT140-positive cells during bone formation.Results In newborn Ift140-creER; R26R(tdTomato) mice, IFT140-positive cells were mainly located in the medullary cavity and then migrated to and differentiated on the surface of trabecular and cortical bone. In contrast, the number of IFT140-positive cells significantly decreased in the adult stage, and these cells were only located in the bone marrow cavity for a short time. In Osx-cre; Ift140(flox/flox) mice, the loss of IFT140 in preosteoblasts caused bone loss in the trabecular bone area at 10 weeks.Conclusion The results revealed that IFT140-positive cells mainly contribute to the early stage of bone formation.