PRX1-positive mesenchymal stem cells drive molar morphogenesis.

IF 10.8 1区 医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE International Journal of Oral Science Pub Date : 2024-02-19 DOI:10.1038/s41368-024-00277-0
Xiaoqiao Xu, Xuyan Gong, Lei Zhang, Han Zhang, Yao Sun
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Abstract

Mammalian teeth, developing inseparable from epithelial-mesenchymal interaction, come in many shapes and the key factors governing tooth morphology deserve to be answered. By merging single-cell RNA sequencing analysis with lineage tracing models, we have unearthed a captivating correlation between the contrasting morphology of mouse molars and the specific presence of PRX1+ cells within M1. These PRX1+ cells assume a profound responsibility in shaping tooth morphology through a remarkable divergence in dental mesenchymal cell proliferation. Deeper into the mechanisms, we have discovered that Wnt5a, bestowed by mesenchymal PRX1+ cells, stimulates mesenchymal cell proliferation while orchestrating molar morphogenesis through WNT signaling pathway. The loss of Wnt5a exhibits a defect phenotype similar to that of siPrx1. Exogenous addition of WNT5A can successfully reverse the inhibited cell proliferation and consequent deviant appearance exhibited in Prx1-deficient tooth germs. These findings bestow compelling evidence of PRX1-positive mesenchymal cells to be potential target in regulating tooth morphology.

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PRX1阳性间充质干细胞驱动臼齿形态发生。
哺乳动物牙齿的发育离不开上皮细胞和间充质细胞的相互作用,它们的形状多种多样,而影响牙齿形态的关键因素也值得探究。通过将单细胞 RNA 测序分析与品系追踪模型相结合,我们发现了小鼠臼齿的对比形态与 M1 中 PRX1+ 细胞的特异性存在之间的惊人关联。这些 PRX1+ 细胞通过牙齿间充质细胞增殖的显著分化,在塑造牙齿形态方面承担着重要责任。深入研究其机制,我们发现间质 PRX1+ 细胞赋予的 Wnt5a 可刺激间质细胞增殖,同时通过 WNT 信号通路协调磨牙的形态发生。缺失 Wnt5a 会表现出与 siPrx1 类似的缺陷表型。外源添加 WNT5A 能成功逆转 Prx1 缺失牙胚的细胞增殖受抑制以及由此产生的异常外观。这些发现有力地证明了 PRX1 阳性间充质细胞是调控牙齿形态的潜在目标。
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来源期刊
International Journal of Oral Science
International Journal of Oral Science DENTISTRY, ORAL SURGERY & MEDICINE-
CiteScore
31.80
自引率
1.30%
发文量
53
审稿时长
>12 weeks
期刊介绍: The International Journal of Oral Science covers various aspects of oral science and interdisciplinary fields, encompassing basic, applied, and clinical research. Topics include, but are not limited to: Oral microbiology Oral and maxillofacial oncology Cariology Oral inflammation and infection Dental stem cells and regenerative medicine Craniofacial surgery Dental material Oral biomechanics Oral, dental, and maxillofacial genetic and developmental diseases Craniofacial bone research Craniofacial-related biomaterials Temporomandibular joint disorder and osteoarthritis The journal publishes peer-reviewed Articles presenting new research results and Review Articles offering concise summaries of specific areas in oral science.
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