Irfan Muhammad, Kim Ji Hyun, Sreekumar Sreelekshmi, Chung Seung
Department of Oral Biology, College of Dentistry, University of Illinois Chicago, Chicago, IL, United States.
Front Genet. 2025 Jun 4;16:1592599. doi: 10.3389/fgene.2025.1592599. eCollection 2025.
Inflammation is a complex host response to harmful infections or injuries, playing beneficial and detrimental roles in tissue regeneration. Notably, clinical dentinogenesis associated with caries development occurs within an inflammatory environment. Reparative dentinogenesis is closely linked to intense inflammation, which triggers the recruitment and differentiation of dental pulp stem cells (DPSCs) into the dentin lineage. Understanding how inflammatory responses influence DPSCs is essential for elucidating the mechanisms underlying dentin and pulp regeneration.
Given the limited data on this process, a broad approach is employed here to understand better the complex mechanisms involved and identify downstream signaling targets. This study investigates the role of inflammation and the complement receptor C5L2 in the odontoblastic differentiation of DPSCs and the associated transcriptomic changes using poly-A RNA sequencing (RNA-seq). RNA-seq techniques provide insight into the transcriptome of a cell, offering higher coverage and greater resolution of its dynamic nature.
Following inflammatory stimulation, DPSCs exhibit significantly altered gene profiles, including marked up-regulation of key odontogenic genes, highlighting the critical role of inflammation in dentinogenesis. We demonstrate that TNFα-treated, odontoblast-like differentiating DPSCs, under C5L2 modulation, show differentially expressed gene profiles and transcriptomic changes.
Beyond quantifying gene expression, RNA-seq data also enable the discovery of novel transcripts, the identification of alternatively spliced genes, and the detection of allele-specific expression. The data presented may offer new avenues for experimental approaches to uncovering pathways in dentinogenesis by identifying specific transcription factors and gene profiles.
炎症是机体对有害感染或损伤的复杂反应,在组织再生中发挥着有益和有害的作用。值得注意的是,与龋齿发展相关的临床牙本质形成发生在炎症环境中。修复性牙本质形成与强烈炎症密切相关,炎症会触发牙髓干细胞(DPSCs)募集并分化为牙本质谱系。了解炎症反应如何影响DPSCs对于阐明牙本质和牙髓再生的潜在机制至关重要。
鉴于关于这一过程的数据有限,本文采用广泛的方法来更好地理解其中涉及的复杂机制,并确定下游信号靶点。本研究使用多聚腺苷酸RNA测序(RNA-seq)研究炎症和补体受体C5L2在DPSCs成牙本质细胞分化及相关转录组变化中的作用。RNA-seq技术可深入了解细胞转录组,对其动态特性提供更高的覆盖范围和分辨率。
炎症刺激后,DPSCs表现出显著改变的基因谱,包括关键牙源性基因的明显上调,突出了炎症在牙本质形成中的关键作用。我们证明,在C5L2调节下,经TNFα处理的、向成牙本质细胞样分化的DPSCs表现出差异表达的基因谱和转录组变化。
除了定量基因表达外,RNA-seq数据还能够发现新的转录本、识别可变剪接基因以及检测等位基因特异性表达。通过识别特定转录因子和基因谱,本文所呈现的数据可能为揭示牙本质形成途径的实验方法提供新途径。