The functional regeneration of the dentin-pulp complex is pivotal for tooth preservation,yet the molecular mechanisms governing odontoblast differentiation remain poorly understood.In the current study,we revealed a d...The functional regeneration of the dentin-pulp complex is pivotal for tooth preservation,yet the molecular mechanisms governing odontoblast differentiation remain poorly understood.In the current study,we revealed a distinct NKD1^(+) subpopulation exhibiting secretory odontoblast characteristics,which was specifically induced in dental pulp stem cells(DPSCs) by Wnt3a,but not by Wnt5a or Wnt10a through single-cell transcriptomic profiling.We then found that the NKD1^(+) subpopulation was functional conservation,which were consistently identified in the odontoblast layers of developing tooth germs in both murine and miniature pig models,as well as within the apical open area in human molars.This conserved spatial distribution and co-localization with DSPP strongly indicates that NKD1^(+) cells were active dentin-secreting odontoblasts.Analysis of gene regulatory networks using SCENIC identified MSX1 as a key transcription factor regulating the specification of NKD1^(+) lineage.Mechanistically,Wnt3a orchestrates a tripartite cascade:upregulating NKD1/MSX1 expression,triggering NKD1 membrane detachment,and facilitating direct NKD1-MSX1interaction to promote MSX1 nuclear translocation.CUT&Tag analysis demonstrated MSX1 occupancy at promoters of odontogenic regulato rs,esta blishing its necessity for odontogenic gene activation.Murine pulp exposure models validated that Wnt3a-activated NKD1-MSX1 signaling significantly enhances reparative dentin formation.This study delineates an evolutionarily conserved Wnt3aNKD1-MSX1 axis that resolves stem cell heterogeneity into functional odontoblast commitment,providing both mechanistic insights into dentin-pulp regeneration and a foundation for targeted regenerative therapies.展开更多
目的:研究MSX1基因外显子区rs13127820(M146L)、rs62636562(A274V)位点多态性与非综合征性唇腭裂(non-syn-dromic cleft lip with or without cleft palate,NSCL/P)的关系。方法:通过聚合酶链反应-限制性片段长度多态性方法,检测243例...目的:研究MSX1基因外显子区rs13127820(M146L)、rs62636562(A274V)位点多态性与非综合征性唇腭裂(non-syn-dromic cleft lip with or without cleft palate,NSCL/P)的关系。方法:通过聚合酶链反应-限制性片段长度多态性方法,检测243例非综合征性唇腭裂(NSCL/P)患者和292例正常对照者全血标本中MSX1基因rs13127820(M146L)、rs62636562(A274V)位点的多态性。结果:MSX1基因位点rs13127820(M146L)、rs62636562(A274V)基因型频率分布符合Hardy-Weinberg平衡;MSX1基因位点rs13127820(M146L)、rs62636562(A274V)等位基因频率分布在NSCL/P组与对照组之间差异有统计学意义(P<0.05)。结论:结果显示MSX1基因位点多态性与NSCL/P的发生有关。展开更多
基金supported by the National Natural Science Foundation of China(82170951,82470961)the Beijing Natural Science Foundation (7222079)+4 种基金the Beijing Hospital Authority"Dengfeng"Talent Training Plan (DFL 20221301)the Beijing Stomatological HospitalCapital Medical University Young Scientist Program (No.YSP202401)the Laboratory for Clinical Medicine and the Central Laboratory of Capital Medical University for their technical support and fundingthe Japan China Sasakawa Medical Fellowship for their generous support and funding。
文摘The functional regeneration of the dentin-pulp complex is pivotal for tooth preservation,yet the molecular mechanisms governing odontoblast differentiation remain poorly understood.In the current study,we revealed a distinct NKD1^(+) subpopulation exhibiting secretory odontoblast characteristics,which was specifically induced in dental pulp stem cells(DPSCs) by Wnt3a,but not by Wnt5a or Wnt10a through single-cell transcriptomic profiling.We then found that the NKD1^(+) subpopulation was functional conservation,which were consistently identified in the odontoblast layers of developing tooth germs in both murine and miniature pig models,as well as within the apical open area in human molars.This conserved spatial distribution and co-localization with DSPP strongly indicates that NKD1^(+) cells were active dentin-secreting odontoblasts.Analysis of gene regulatory networks using SCENIC identified MSX1 as a key transcription factor regulating the specification of NKD1^(+) lineage.Mechanistically,Wnt3a orchestrates a tripartite cascade:upregulating NKD1/MSX1 expression,triggering NKD1 membrane detachment,and facilitating direct NKD1-MSX1interaction to promote MSX1 nuclear translocation.CUT&Tag analysis demonstrated MSX1 occupancy at promoters of odontogenic regulato rs,esta blishing its necessity for odontogenic gene activation.Murine pulp exposure models validated that Wnt3a-activated NKD1-MSX1 signaling significantly enhances reparative dentin formation.This study delineates an evolutionarily conserved Wnt3aNKD1-MSX1 axis that resolves stem cell heterogeneity into functional odontoblast commitment,providing both mechanistic insights into dentin-pulp regeneration and a foundation for targeted regenerative therapies.
文摘目的:研究MSX1基因外显子区rs13127820(M146L)、rs62636562(A274V)位点多态性与非综合征性唇腭裂(non-syn-dromic cleft lip with or without cleft palate,NSCL/P)的关系。方法:通过聚合酶链反应-限制性片段长度多态性方法,检测243例非综合征性唇腭裂(NSCL/P)患者和292例正常对照者全血标本中MSX1基因rs13127820(M146L)、rs62636562(A274V)位点的多态性。结果:MSX1基因位点rs13127820(M146L)、rs62636562(A274V)基因型频率分布符合Hardy-Weinberg平衡;MSX1基因位点rs13127820(M146L)、rs62636562(A274V)等位基因频率分布在NSCL/P组与对照组之间差异有统计学意义(P<0.05)。结论:结果显示MSX1基因位点多态性与NSCL/P的发生有关。
