干旱区生态环境知识资源中心(Arid): Functionally Distinctive Ptch Receptors Establish Multimodal Hedgehog Signaling in the Tooth Epithelial Stem Cell Niche

Arid

DOI	10.1002/stem.3042
	Functionally Distinctive Ptch Receptors Establish Multimodal Hedgehog Signaling in the Tooth Epithelial Stem Cell Niche
	Binder, Martin 1; Chmielarz, Piotr 1,2; Mckinnon, Peter J.3; Biggs, Leah C.1; Thesleff, Irma 1; Balic, Anamaria 1
通讯作者	Balic, Anamaria
来源期刊	STEM CELLS
ISSN	1066-5099
EISSN	1549-4918
出版年	2019
卷号	37 期号:9 页码:1238-1248
英文摘要	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 (P-cadherin, Sonic Hedgehog, 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 Desert Hedgehog, 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. Stem Cells 2019;37:1238-1248
英文关键词	Tooth epithelial stem cells Stem cell niche Cervical loop Hedgehog Patched
类型	Article
语种	英语
国家	Finland ; Poland ; USA
开放获取类型	Green Accepted, Bronze
收录类别	SCI-E
WOS记录号	WOS:000482967700012
WOS关键词	SONIC-HEDGEHOG ; PERIPHERAL-NERVES ; SHH ; EXPRESSION ; GENE ; PROLIFERATION ; MAINTENANCE ; HOMEOSTASIS ; INHIBITION ; APOPTOSIS
WOS类目	Cell & Tissue Engineering ; Biotechnology & Applied Microbiology ; Oncology ; Cell Biology ; Hematology
WOS研究方向	Cell Biology ; Biotechnology & Applied Microbiology ; Oncology ; Hematology
资源类型	期刊论文
条目标识符	http://119.78.100.177/qdio/handle/2XILL650/218935
作者单位	1.Univ Helsinki, Inst Biotechnol, Res Program Dev Biol, Helsinki, Finland; 2.Polish Acad Sci, Inst Pharmacol, Dept Brain Biochem, Krakow, Poland; 3.St Jude Childrens Res Hosp, Dept Genet, 332 N Lauderdale St, Memphis, TN 38105 USA
推荐引用方式 GB/T 7714	Binder, Martin,Chmielarz, Piotr,Mckinnon, Peter J.,et al. Functionally Distinctive Ptch Receptors Establish Multimodal Hedgehog Signaling in the Tooth Epithelial Stem Cell Niche[J],2019,37(9):1238-1248.
APA	Binder, Martin,Chmielarz, Piotr,Mckinnon, Peter J.,Biggs, Leah C.,Thesleff, Irma,&Balic, Anamaria.(2019).Functionally Distinctive Ptch Receptors Establish Multimodal Hedgehog Signaling in the Tooth Epithelial Stem Cell Niche.STEM CELLS,37(9),1238-1248.
MLA	Binder, Martin,et al."Functionally Distinctive Ptch Receptors Establish Multimodal Hedgehog Signaling in the Tooth Epithelial Stem Cell Niche".STEM CELLS 37.9(2019):1238-1248.