International Graduate Program in Geriatric Dentistry and Special Patients Care, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand.
Center of Excellence in Genomics and Precision Dentistry, Department of Physiology, Faculty of Dentistry, Chulalongkorn University, Bangkok, 10330, Thailand.
Sci Rep. 2022 May 25;12(1):8860. doi: 10.1038/s41598-022-12867-1.
The molecular control of tooth development is different between the maxilla and mandible, contributing to different tooth shapes and locations; however, whether this difference occurs in human permanent teeth is unknown. The aim of this study was to investigate and compare the transcriptome profiles of permanent maxillary and mandibular posterior teeth. Ten participants who had a pair of opposing premolars or molars extracted were recruited. The RNA obtained from cultured dental pulp stem cells underwent RNA-sequencing and qRT-PCR. The transcriptome profiles of two opposing premolar pairs and two molar pairs demonstrated that the upper premolars, lower premolars, upper molars, and lower molars expressed the same top-ranked genes, comprising FN1, COL1A1, COL1A2, ACTB, and EEFIA1, which are involved in extracellular matrix organization, immune system, signal transduction, hemostasis, and vesicle-mediated transport. Comparative transcriptome analyses of each/combined tooth pairs demonstrated that PITX1 was the only gene with different expression levels between upper and lower posterior teeth. PITX1 exhibited a 64-fold and 116-fold higher expression level in lower teeth compared with their upper premolars and molars, respectively. These differences were confirmed by qRT-PCR. Taken together, this study, for the first time, reveals that PITX1 is expressed significantly higher in mandibular posterior teeth compared with maxillary posterior teeth. The difference is more evident in the molars compared with premolars and consistent with its expression pattern in mouse developing teeth. We demonstrate that differences in lower versus upper teeth gene expression during odontogenesis occur in permanent teeth and suggest that these differences should be considered in molecular studies of dental pulp stem cells. Our findings pave the way to develop a more precise treatment in regenerative dentistry such as gene-based therapies for dentin/pulp regeneration and regeneration of different tooth types.
牙齿发育的分子控制在上颌骨和下颌骨之间不同，导致牙齿形状和位置不同；然而，这种差异是否发生在人类恒牙中尚不清楚。本研究旨在研究和比较人恒牙上颌和下颌后牙的转录组谱。招募了 10 名参与者，他们有一对相对的前磨牙或磨牙被拔出。从培养的牙髓干细胞中获得的 RNA 进行了 RNA-seq 和 qRT-PCR。两对相对的前磨牙和两对磨牙的转录组谱表明，上颌前磨牙、下颌前磨牙、上颌磨牙和下颌磨牙表达相同的顶级基因，包括 FN1、COL1A1、COL1A2、ACTB 和 EEFIA1，这些基因参与细胞外基质组织、免疫系统、信号转导、止血和小泡介导的运输。对每个/联合牙对的比较转录组分析表明，PITX1 是上、下后牙之间唯一表达水平不同的基因。与上颌前磨牙和磨牙相比，PITX1 在下颌牙齿中的表达水平分别高出 64 倍和 116 倍。qRT-PCR 验证了这些差异。总之，本研究首次揭示了 PITX1 在下颌后牙中的表达明显高于上颌后牙。磨牙中的差异比前磨牙中更明显，与小鼠发育牙齿中的表达模式一致。我们证明，在牙发生过程中，下牙与上牙基因表达的差异发生在恒牙中，并表明在牙髓干细胞的分子研究中应考虑这些差异。我们的发现为再生牙科中的更精确治疗铺平了道路，例如牙本质/牙髓再生和不同牙齿类型再生的基因治疗。
