Abstract：
Epigenetic regulation plays important role in stem cell maintenance. Ptip was identified as epigenetic regulator, but the role in dental progenitor cells remains unclear.
Dental mesenchymal progenitor cells were targeted by Sp7-icre and visualized in mTmG; Sp7-icre mice. The Ptipf/f; Sp7-icre mice were generated and the phenotype of incisors and molars were shown by micro-computerized tomography, scanning electron microscope, hematoxylin & eosin staining, and immunofluorescence. Dental mesenchymal progenitor cells were sorted by fluorescence-activated cell sorting from lower incisors and RNA sequencing was performed.
The Sp7-icre targets dental mesenchymal progenitor cells in incisors and molars. The Ptipf/f; Sp7-icre mice showed spontaneous fractures in the cusp of upper incisors and lower incisors at 3 weeks (w), compensative overgrowth of lower incisors at 1 month (M), and overgrowth extended to the outside at 2 M. The molars showed shortened roots. The functions of odontoblasts and dental mesenchymal progenitor cells were impaired. Mechanically, loss of Ptip activates the Wnt pathway and upregulates the expression of Wls in dental mesenchymal progenitor cells. Also, the regenerative ability of lower incisors was significantly impaired.
We first demonstrated that Ptip was crucial for tooth development via regulating Wnt signaling.
Dental mesenchymal progenitor cells were targeted by Sp7-icre and visualized in mTmG; Sp7-icre mice. The Ptipf/f; Sp7-icre mice were generated and the phenotype of incisors and molars were shown by micro-computerized tomography, scanning electron microscope, hematoxylin & eosin staining, and immunofluorescence. Dental mesenchymal progenitor cells were sorted by fluorescence-activated cell sorting from lower incisors and RNA sequencing was performed.
The Sp7-icre targets dental mesenchymal progenitor cells in incisors and molars. The Ptipf/f; Sp7-icre mice showed spontaneous fractures in the cusp of upper incisors and lower incisors at 3 weeks (w), compensative overgrowth of lower incisors at 1 month (M), and overgrowth extended to the outside at 2 M. The molars showed shortened roots. The functions of odontoblasts and dental mesenchymal progenitor cells were impaired. Mechanically, loss of Ptip activates the Wnt pathway and upregulates the expression of Wls in dental mesenchymal progenitor cells. Also, the regenerative ability of lower incisors was significantly impaired.
We first demonstrated that Ptip was crucial for tooth development via regulating Wnt signaling.
摘要：
目的：表观遗传调控在干细胞维持中起重要作用。Ptip被确定为表观遗传调节剂，但在牙齿祖细胞中的作用尚不清楚.
方法：通过Sp7-icre靶向牙齿间充质祖细胞，并在mTmG;Sp7-icre小鼠中可视化。产生Ptipf/f;Sp7-icre小鼠，并通过显微计算机断层扫描显示切牙和磨牙的表型，扫描电子显微镜，hoxylin和伊红染色和免疫荧光。通过荧光激活细胞分选从下切牙分选牙齿间充质祖细胞并进行RNA测序。
结果：Sp7-icre靶向切牙和磨牙中的牙间充质祖细胞。Ptipf/f;Sp7-icre小鼠在三周（w）时在上切牙和下切牙的尖端出现自发性骨折，在一个月（M）时，下切牙的补偿性过度生长，2M时过度生长到外部。磨牙显示根缩短。成牙本质细胞和牙间充质祖细胞的功能受损。机械上,Ptip的缺失激活Wnt通路并上调Wls在牙间充质祖细胞中的表达。此外，下切牙的再生能力明显受损。
结论：我们首先证明了Ptip通过调节Wnt信号对牙齿发育至关重要。
方法：通过Sp7-icre靶向牙齿间充质祖细胞，并在mTmG;Sp7-icre小鼠中可视化。产生Ptipf/f;Sp7-icre小鼠，并通过显微计算机断层扫描显示切牙和磨牙的表型，扫描电子显微镜，hoxylin和伊红染色和免疫荧光。通过荧光激活细胞分选从下切牙分选牙齿间充质祖细胞并进行RNA测序。
结果：Sp7-icre靶向切牙和磨牙中的牙间充质祖细胞。Ptipf/f;Sp7-icre小鼠在三周（w）时在上切牙和下切牙的尖端出现自发性骨折，在一个月（M）时，下切牙的补偿性过度生长，2M时过度生长到外部。磨牙显示根缩短。成牙本质细胞和牙间充质祖细胞的功能受损。机械上,Ptip的缺失激活Wnt通路并上调Wls在牙间充质祖细胞中的表达。此外，下切牙的再生能力明显受损。
结论：我们首先证明了Ptip通过调节Wnt信号对牙齿发育至关重要。
