摘要
研究人员对牙发育过程中的高分辨时-空关系仍然知之甚少.该文通过高通量(92,688个细胞)单细胞RNA测序追踪牙胚发育过程的细胞轨迹,并结合ATAC测序技术,明确牙胚间充质细胞具显著区分牙齿类型的特异性特征.该文同时发掘起源于间充质细胞的牙本质和牙髓形成中的关键基因调控网络,并绘制具有成牙潜能的间充质细胞空间模式图.在此基础上,该文发现了分别分布于发育晚期牙乳头上半部和预成牙本质细胞层的两个牙胚间充质细胞群,即CD24^(+)和Plac8^(+)细胞,并解析了这两群细胞均可高效诱导非牙源性上皮细胞共同成牙的生理功能.值得关注的是其中的Plac8^(+)组织是迄今为止被证实能在体外诱导再生牙形成的含细胞数量最少且异质性最低的间充质组织模块.综上,该文的工作揭示了牙胚发育过程中由结构和功能决定的时空模式和细胞异质性,为基于干细胞的再生牙构建提供重要的理论基础.
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.
作者
王曜峰
赵艺帆
陈树彬
陈小明
张燕梅
陈红
廖远松
张嘉书
吴迪
褚洪星
黄红英
吴彩霞
黄仕娟
徐慧超
贾蓓
刘洁
冯波
李中瀚
秦大江
裴端卿
蔡景蕾
Yaofeng Wang;Yifan Zhao;Shubin Chen;Xiaoming Chen;Yanmei Zhang;Hong Chen;Yuansong Liao;Jiashu Zhang;Di Wu;Hongxing Chu;Hongying Huang;Caixia Wu;Shijuan Huang;Huichao Xu;Bei Jia;Jie Liu;Bo Feng;Zhonghan Li;Dajiang Qin;Duanqing Pei;Jinglei Cai(Innovation Centre for Advanced Interdisciplinary Medicine,The Fifth Affiliated Hospital of Guangzhou Medical University,Guangzhou 510799,China;CAS Key Laboratory of Regenerative Biology,GIBH-CUHK Joint Research Laboratory on Stem Cell and Regenerative Medicine,Guangzhou Institutes of Biomedicine and Health,Chinese Academy of Sciences,Guangzhou 510530,China;Centre for Regenerative Medicine and Health,Hong Kong Institute of Science&Innovation,Chinese Academy of Sciences,Hong Kong,China;Bioland Laboratory,Guangzhou Regenerative Medicine and Health Guangdong Laboratory,Guangzhou 510005,China;Guangdong Provincial People’s Hospital Ganzhou Hospital,Ganzhou Municipal Hospital,Ganzhou 341099,China;State Key Laboratory of Oral Disease,West China Hospital of Stomatology,Center of Growth Metabolism and Aging,Key Laboratory of Bio-Resource and Eco-Environment of Ministry of Education,College of Life Sciences,Sichuan University,Chengdu 610041,China;Department of Regeneration Medicine,School of Pharmaceutical Science,Jilin University,Changchun 130012,China;Department of Periodontics and Implantology,Stomatological Hospital,Southern Medical University(Guangdong Provincial Stomatological Hospital),Guangzhou 510515,China;Animal Center,Guangzhou Institutes of Biomedicine and Health,Chinese Academy of Sciences,Guangzhou 510530,China;The Center for Prenatal and Hereditary Disease Diagnosis,Department of Obstetrics and Gynecology,Nanfang Hospital,Southern Medical University,Guangzhou 510515,China;Department of Obstetrics and Gynecology,Nanfang Hospital,Southern Medical University,Guangzhou 510515,China;School of Biomedical Sciences,The Chinese University of Hong Kong,Hong Kong SAR,China;Laboratory of Cell Fate Control,School of Life Sciences,Westlake University,Hangzhou 310024,China)
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
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)。
关键词
CD24
间充质
牙胚发育
细胞群
基因调控网络
时空模式
牙发育
牙本质
Single cell RNA-seq
Dental germ development
Spatiotemporal pattern
Odontogenesis
CD24^(+)odontogenic cells
Plac8^(+)odontogenic cells
