Functionally Distinctive Ptch Receptors Establish Multimodal Hedgehog Signaling in the Tooth Epithelial Stem Cell Niche.
Functionally Distinctive Ptch Receptors Establish Multimodal Hedgehog Signaling in the Tooth Epithelial Stem Cell Niche.
复制标题
功能独特的PTCH受体在牙齿上皮干细胞生态位中建立了多模式刺猬信号传导。
DOI：
10.1002/stem.3042
复制
发表时间：
2019-09
期刊：
影响因子：
--
通讯作者：
Balic A
中科院分区：
文献类型：
--
作者：
Binder M;Chmielarz P;Mckinnon PJ;Biggs LC;Thesleff I;Balic A
小鼠门牙的持续生长是由于上皮干细胞（SCs）在其称为颈环（CL）的生态位中终身维持。几个信号因子调节SC的维持和/或它们的分化以实现器官稳态。先前的研究表明，Hedgehog信号传导对于sc在生态位中的维持以及它们的分化都是至关重要的。在CL的限制下，Hedgehog信号如何调节这两种相反的细胞行为仍然是难以捉摸的。在这项研究中，我们使用体外器官和细胞培养来药理学上减弱Hedgehog信号。我们分析了SC生态位中表达的各种基因的表达，以确定Hedgehog信号通路改变对生态位内细胞等级的影响。这些基因包括SCs （Sox2和Lgr5）和转运扩增细胞（TACs, P-cadherin， Shh和Yap）的标记。我们的研究结果表明，Hedgehog信号是SC在生态位中生存的关键因素，并且SC生态位的结构和多样性受到多个Hedgehog配体的调节。我们证明了另一个Hedgehog配体的存在，神经源性Dhh，分泌在CL附近。此外，我们提供的证据表明，Hedgehog受体Ptch1和Ptch2引发独立的反应，使多模态Hedgehog信号传导同时调节SC的维持和分化。我们的研究表明，连续生长的门牙中的细胞等级是两个Hedgehog配体与功能不同的Ptch受体复杂相互作用的结果。
Continuous growth of the mouse incisor teeth is due to the life-long maintenance of epithelial stem cells (SCs) in their niche called cervical loop (CL). Several signaling factors regulate SC maintenance and/or their differentiation to achieve organ homeostasis. Previous studies indicated that Hedgehog signaling is crucial for both the maintenance of the SCs in the niche, as well as for their differentiation. How Hedgehog signaling regulates these two opposing cellular behaviors within the confinement of the CL remains elusive. In this study we used in vitro organ and cell cultures to pharmacologically attenuate Hedgehog signaling. We analyzed expression of various genes expressed in the SC niche to determine the effect of altered Hedgehog signaling on the cellular hierarchy within the niche. These genes include markers of SCs (Sox2 and Lgr5) and transit-amplifying cells (TACs, P-cadherin, Shh and Yap). Our results show that Hedgehog signaling is a critical survival factor for SCs in the niche, and that the architecture and the diversity of the SC niche are regulated by multiple Hedgehog ligands. We demonstrated the presence of an additional Hedgehog ligand, nerve-derived Dhh, secreted in the proximity of the CL. In addition, we provide evidence that Hedgehog receptors Ptch1 and Ptch2 elicit independent responses which enable multimodal Hedgehog signaling to simultaneously regulate SC maintenance and differentiation. Our study indicates that the cellular hierarchy in the continuously growing incisor is a result of complex interplay of two Hedgehog ligands with functionally distinct Ptch receptors.
登录
查看更多内容
影响因子：
6.5
作者：
Adolphe, Christelle;Nieuwenhuis, Erica;Wainwright, Brandon J.
通讯作者：
Wainwright, Brandon J.
影响因子：
5.3
作者：
Nieuwenhuis, Erica;Motoyama, Jun;Hui, Chi-chung
通讯作者：
Hui, Chi-chung
DOI：
10.1007/978-1-62703-989-5_11
发表时间：
2014-01-01
期刊：
SKELETAL DEVELOPMENT AND REPAIR: METHODS AND PROTOCOLS
影响因子：
--
作者：
Kawamoto, Tadafumi;Kawamoto, Komei
通讯作者：
Kawamoto, Komei
影响因子：
11.2
作者：
Lee, Youngsoo;Miller, Heather L.;McKinnon, Peter J.
通讯作者：
McKinnon, Peter J.
影响因子：
4.6
作者：
Gritli-Linde, A;Bei, M;McMahon, AP
通讯作者：
McMahon, AP