The spatiotemporal relationships in high-resolution during odontogenesis remain poorly understood.We report a cell lineage and atlas of developing mouse teeth.We performed a large-scale(92,688 cells)single cell RNA se...The spatiotemporal relationships in high-resolution during odontogenesis remain poorly understood.We report a cell lineage and atlas of developing mouse teeth.We performed a large-scale(92,688 cells)single cell RNA sequencing,tracing the cell trajectories during odontogenesis from embryonic days 10.5 to 16.5.Combined with an assay for transposase-accessible chromatin with high-throughput sequencing,our results suggest that mesenchymal cells show the specific transcriptome profiles to distinguish the tooth types.Subsequently,we identified key gene regulatory networks in teeth and bone formation and uncovered spatiotemporal patterns of odontogenic mesenchymal cells.CD24^(+)and Plac8^(+)cells from the mesenchyme at the bell stage were distributed in the upper half and preodontoblast layer of the dental papilla,respectively,which could individually induce nonodontogenic epithelia to form tooth-like structures.Specifically,the Plac8^(+)tissue we discovered is the smallest piece with the most homogenous cells that could induce tooth regeneration to date.Our work reveals previously unknown heterogeneity and spatiotemporal patterns of tooth germs that may lead to tooth regeneration for regenerative dentistry.展开更多
Dentin matrix protein 1（DMP1） is essential to odontogenesis. Its mutations in human subjects lead to dental problems such as dental deformities, hypomineralization and periodontal impairment. Primarily, DMP1 is cons...Dentin matrix protein 1（DMP1） is essential to odontogenesis. Its mutations in human subjects lead to dental problems such as dental deformities, hypomineralization and periodontal impairment. Primarily, DMP1 is considered as an extracellular matrix protein that promotes hydroxyapatite formation and activates intracellular signaling pathway via interacting with avb3 integrin. Recent in vitro studies suggested that DMP1 might also act as a transcription factor. In this study, we examined whether full-length DMP1 could function as a transcription factor in the nucleus and regulate odontogenesis in vivo. We first demonstrated that a patient with the DMP1M1 V mutation, which presumably causes a loss of the secretory DMP1 but does not affect the nuclear translocation of DMP1, shows a typical rachitic tooth defect. Furthermore, we generated transgenic mice expressingNLSDMP1, in which the endoplasmic reticulum（ER） entry signal sequence of DMP1 was replaced by a nuclear localization signal（NLS） sequence, under the control of a 3.6 kb rat type I collagen promoter plus a 1.6 kb intron 1. We then crossbred theNLSDMP1 transgenic mice with Dmp1 null mice to express the NLSDMP1 in Dmp1-deficient genetic background. Although immunohistochemistry demonstrated thatNLSDMP1 was localized in the nuclei of the preodontoblasts and odontoblasts, the histological, morphological and biochemical analyses showed that it failed to rescue the dental and periodontal defects as well as the delayed tooth eruption in Dmp1 null mice. These data suggest that the full-length DMP1 plays no apparent role in the nucleus during odontogenesis.展开更多
This study aimed to compare epithelial cells derived from human embryonic stem cells(hESCs) to human ameloblast-lineage cells (ALCs),as a way to determine their potential use as a cell source for ameloblast regenerati...This study aimed to compare epithelial cells derived from human embryonic stem cells(hESCs) to human ameloblast-lineage cells (ALCs),as a way to determine their potential use as a cell source for ameloblast regeneration.Induced by various concentrations of bone morphogenetic protein 4(BMP4),retinoic acid(RA) and lithium chloride(LiCI) for 7 days,hESCs adopted cobble-stone epithelial phenotype(hESC-derived epithelial cells(ES-ECs)) and expressed cytokeratin 14.Compared with ALCs and oral epithelial cells(OE), ES-ECs expressed amelogenesis-associated genes similar to ALCs.ES-ECs were compared with human fetal skin epithelium,human fetal oral buccal mucosal epithelial cells and human ALCs for their expression pattern of cytokeratins as well.ALCs had relatively high expression levels of cytokeratin 76,which was also found to be upregulated in ES-ECs.Based on the present study,with the similarity of gene expression with ALCs,ES-ECs are a promising potential cell source for regeneration,which are not available in erupted human teeth for regeneration of enamel.展开更多
Within the nervous system, regeneration is limited, and this is due to the small amount of neural stem cells, the inhibitory origin of the stem cell niche and often to the development of a scar which constitutes a mec...Within the nervous system, regeneration is limited, and this is due to the small amount of neural stem cells, the inhibitory origin of the stem cell niche and often to the development of a scar which constitutes a mechanical barrier for the regeneration. Regarding these aspects, many efforts have been done in the re- search of a cell component that combined with scaffolds and growth factors could be suitable for nervous regeneration in regenerative medicine approaches. Autologous mesenchymal stem cells represent nowa- days the ideal candidate for this aim, thank to their multipotency and to their amount inside adult tissues. However, issues in their harvesting, through the use of invasive techniques, and problems involved in their ageing, require the research of new autologous sources. To this purpose, the recent discovery of a stem cells component in teeth, and which derive from neural crest cells, has came to the light the possibility of using dental stem cells in nervous system regeneration. In this work, in order to give guidelines on the use of dental stem cells for neural regeneration, we briefly introduce the concepts of regeneration and regenerative medicine, we then focus the attention on odontogenesis, which involves the formation and the presence of a stem component in different parts of teeth, and finally we describe some experimental approaches which are exploiting dental stem cells for neural studies.展开更多
Family with sequence similarity 20, member C （FAM20C） 又称牙本质基质蛋白4（DMP4），是一种分泌性钙结合激酶，在矿化组织中高表达，可使生物矿化相关的分泌性钙结合磷酸蛋白（scPPs）家族磷酸化，调控磷酸钙沉积，形成并影响羟...Family with sequence similarity 20, member C （FAM20C） 又称牙本质基质蛋白4（DMP4），是一种分泌性钙结合激酶，在矿化组织中高表达，可使生物矿化相关的分泌性钙结合磷酸蛋白（scPPs）家族磷酸化，调控磷酸钙沉积，形成并影响羟基磷灰石晶体的生长和排列。FAM20C突变可致Raine综合征（又称硬化性骨发育不良），导致骨、牙发育缺陷，低磷酸血症等，新生儿致死率高。近年来研究表明，FAM20C可促进成骨细胞、成釉细胞及成牙本质细胞分化，负性调控成纤维细胞生长因子23（FGF23）影响血磷稳态，在骨和牙齿发育矿化中发挥重要作用。就FAM20C在骨和牙发育矿化中的研究现状作一综述。展开更多
基金supported by the National Key Research and Development Program of China Stem Cell and Translational Research,China(2017YFA0104800)the Research Funds from Health@InnoHK Program launched by Innovation Technology Commission of the Hong Kong SAR,China+4 种基金National Natural Science Foundation of China(81570944 and 92068201)Science and Technology Planning Project of Guangdong Province,China(2020B1212060052)High-level Hospital Construction Project(DFJHBF202110)Youth Innovation Promotion of the Chinese Academy of Sciences(2019348)Guangzhou Key Medical Disciplines(2021–2023)。
文摘The spatiotemporal relationships in high-resolution during odontogenesis remain poorly understood.We report a cell lineage and atlas of developing mouse teeth.We performed a large-scale(92,688 cells)single cell RNA sequencing,tracing the cell trajectories during odontogenesis from embryonic days 10.5 to 16.5.Combined with an assay for transposase-accessible chromatin with high-throughput sequencing,our results suggest that mesenchymal cells show the specific transcriptome profiles to distinguish the tooth types.Subsequently,we identified key gene regulatory networks in teeth and bone formation and uncovered spatiotemporal patterns of odontogenic mesenchymal cells.CD24^(+)and Plac8^(+)cells from the mesenchyme at the bell stage were distributed in the upper half and preodontoblast layer of the dental papilla,respectively,which could individually induce nonodontogenic epithelia to form tooth-like structures.Specifically,the Plac8^(+)tissue we discovered is the smallest piece with the most homogenous cells that could induce tooth regeneration to date.Our work reveals previously unknown heterogeneity and spatiotemporal patterns of tooth germs that may lead to tooth regeneration for regenerative dentistry.
基金supported by NIH grants DE018486 and R56 DE022789 to Jian-Quan Feng, DE023365 to Yong-Bo Lu and a scholarship from the Chinese State Scholarship Fund to Shu-Xian Lin (2010627108)
文摘Dentin matrix protein 1（DMP1） is essential to odontogenesis. Its mutations in human subjects lead to dental problems such as dental deformities, hypomineralization and periodontal impairment. Primarily, DMP1 is considered as an extracellular matrix protein that promotes hydroxyapatite formation and activates intracellular signaling pathway via interacting with avb3 integrin. Recent in vitro studies suggested that DMP1 might also act as a transcription factor. In this study, we examined whether full-length DMP1 could function as a transcription factor in the nucleus and regulate odontogenesis in vivo. We first demonstrated that a patient with the DMP1M1 V mutation, which presumably causes a loss of the secretory DMP1 but does not affect the nuclear translocation of DMP1, shows a typical rachitic tooth defect. Furthermore, we generated transgenic mice expressingNLSDMP1, in which the endoplasmic reticulum（ER） entry signal sequence of DMP1 was replaced by a nuclear localization signal（NLS） sequence, under the control of a 3.6 kb rat type I collagen promoter plus a 1.6 kb intron 1. We then crossbred theNLSDMP1 transgenic mice with Dmp1 null mice to express the NLSDMP1 in Dmp1-deficient genetic background. Although immunohistochemistry demonstrated thatNLSDMP1 was localized in the nuclei of the preodontoblasts and odontoblasts, the histological, morphological and biochemical analyses showed that it failed to rescue the dental and periodontal defects as well as the delayed tooth eruption in Dmp1 null mice. These data suggest that the full-length DMP1 plays no apparent role in the nucleus during odontogenesis.
基金supported by NIH/NIDCR grants R03 DE019507-02 to Yan Zhang,R21 D E0 18633 to Pamela K DenBesten and 2011SCU 11999-3/ NSFC81200760to Li-Wei Zheng
文摘This study aimed to compare epithelial cells derived from human embryonic stem cells(hESCs) to human ameloblast-lineage cells (ALCs),as a way to determine their potential use as a cell source for ameloblast regeneration.Induced by various concentrations of bone morphogenetic protein 4(BMP4),retinoic acid(RA) and lithium chloride(LiCI) for 7 days,hESCs adopted cobble-stone epithelial phenotype(hESC-derived epithelial cells(ES-ECs)) and expressed cytokeratin 14.Compared with ALCs and oral epithelial cells(OE), ES-ECs expressed amelogenesis-associated genes similar to ALCs.ES-ECs were compared with human fetal skin epithelium,human fetal oral buccal mucosal epithelial cells and human ALCs for their expression pattern of cytokeratins as well.ALCs had relatively high expression levels of cytokeratin 76,which was also found to be upregulated in ES-ECs.Based on the present study,with the similarity of gene expression with ALCs,ES-ECs are a promising potential cell source for regeneration,which are not available in erupted human teeth for regeneration of enamel.
文摘Within the nervous system, regeneration is limited, and this is due to the small amount of neural stem cells, the inhibitory origin of the stem cell niche and often to the development of a scar which constitutes a mechanical barrier for the regeneration. Regarding these aspects, many efforts have been done in the re- search of a cell component that combined with scaffolds and growth factors could be suitable for nervous regeneration in regenerative medicine approaches. Autologous mesenchymal stem cells represent nowa- days the ideal candidate for this aim, thank to their multipotency and to their amount inside adult tissues. However, issues in their harvesting, through the use of invasive techniques, and problems involved in their ageing, require the research of new autologous sources. To this purpose, the recent discovery of a stem cells component in teeth, and which derive from neural crest cells, has came to the light the possibility of using dental stem cells in nervous system regeneration. In this work, in order to give guidelines on the use of dental stem cells for neural regeneration, we briefly introduce the concepts of regeneration and regenerative medicine, we then focus the attention on odontogenesis, which involves the formation and the presence of a stem component in different parts of teeth, and finally we describe some experimental approaches which are exploiting dental stem cells for neural studies.
文摘Family with sequence similarity 20, member C （FAM20C） 又称牙本质基质蛋白4（DMP4），是一种分泌性钙结合激酶，在矿化组织中高表达，可使生物矿化相关的分泌性钙结合磷酸蛋白（scPPs）家族磷酸化，调控磷酸钙沉积，形成并影响羟基磷灰石晶体的生长和排列。FAM20C突变可致Raine综合征（又称硬化性骨发育不良），导致骨、牙发育缺陷，低磷酸血症等，新生儿致死率高。近年来研究表明，FAM20C可促进成骨细胞、成釉细胞及成牙本质细胞分化，负性调控成纤维细胞生长因子23（FGF23）影响血磷稳态，在骨和牙齿发育矿化中发挥重要作用。就FAM20C在骨和牙发育矿化中的研究现状作一综述。
