Identification and Characterization of Endogenous Dental Pulp Stem Cells

内源性牙髓干细胞的鉴定和表征

• 批准号: 10409267
• 负责人: Takamitsu Maruyama
• 金额: $ 28.32万
• 依托单位: ADA FORSYTH INSTITUTE, INC.
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-06-01 至 2023-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10409267
• 关键词: Adult; Bioinformatics; Biological Assay; Biological Models; Calvaria; Cell Lineage; Cells; Clinical; Data; Dental; Dental Pulp; Dentin Formation; Discipline; Disease; Endodontics; Genetic; Goals; Gold; Heterogeneity; Homeostasis; Human; Incisor; Label; Maintenance; Modeling; Mouse Strains; Mus; Natural regeneration; Odontoblasts; Population; Process; Property; RNA Sequence Analysis; Regenerative capacity; Research; Source; Stem cell transplant; Testing; Tissues; Tooth structure; Transplantation; WNT Signaling Pathway; adult stem cell; angiogenesis; beta catenin; bone; cell type; dental transplantation; design; in vivo; knowledge base; mouse model; novel strategies; regenerative; regenerative therapy; response; self-renewal; single-cell RNA sequencing; skeletal stem cell; stem cell biology; stem cell population; stem cells; stemness; tissue regeneration; tool; transcriptome

Title Identification and characterization of endogenous dental pulp stem cells Abstract The goal of this proposal is to identify and characterize endogenous dental pulp stem cells (DPSCs) in adult mice molars. Although continuously growing mouse incisors have been used as a model system to characterize dental stem cells, endogenous DPSCs within the molars remain understudied. Unlike incisors, mouse molars are not continuously growing and resemble human teeth. Therefore, it is crucial for the field of stem cell biology as well as dental pulp regeneration therapy to identify and characterize endogenous DPSCs isolated from the molars. To conduct this research we have developed a mouse model in which Axin2+ dental pulp cells in molars are genetically labeled. Our preliminary assessment shows that Axin2+ DPSCs are capable of self-renewing and differentiating into mature odontoblasts for a year in vivo. In addition, the transplanted dental pulp cells are capable regenerate pulp-like tissue. This initial discovery shows a difference in the type of tissues regenerated from other adult stem cells and DPSCs, suggesting their unique cellular plasticity present in endogenous DPSCs. In this application, we will test if Axin2-expressing DPSCs can meet the criteria of adult stem cells. We will also examine the stem cells properties at a single cell level. The regenerative ability and cellular plasticity of the transplanted endogenous DPSCs will be carefully assessed. Potential heterogeneity of Axin2+ DPSCs will be identified through single-cell RNA-sequence analysis and bioinformatics analysis. The completion of this proposal has outstanding potential to advance our knowledge base of endogenous DPSCs in molars, leading to novel strategies for tissue regeneration therapies.

标题 内源性牙髓干细胞的鉴定与鉴定 摘要 本研究的目的是鉴定和鉴定成人牙髓干细胞（DPSC）， 老鼠的臼齿尽管连续生长的小鼠门牙已被用作模型系统， 尽管目前对牙齿干细胞的研究还不成熟，但磨牙中的内源性DPSC仍处于研究阶段。与门牙不同， 老鼠的臼齿不是连续生长的，类似于人类的牙齿。因此，这对该领域至关重要， 干细胞生物学以及牙髓再生治疗来鉴定和表征内源性DPSC 从臼齿上分离出来为了进行这项研究，我们开发了一种小鼠模型，其中Axin2+牙科 臼齿中的牙髓细胞被基因标记。我们的初步评估显示Axin2+ DPSC是 能够自我更新并在体内分化为成熟的成牙本质细胞一年。此外该 移植的牙髓细胞能够再生牙髓样组织。这一初步发现表明 在从其他成体干细胞和DPSC再生的组织类型中， 存在于内源性DPSC中的可塑性。在本申请中，我们将测试表达Axin2的DPSC是否可以满足 成体干细胞的标准。我们还将在单细胞水平上研究干细胞的特性。的 将仔细评估移植的内源性DPSC的再生能力和细胞可塑性。 Axin2+ DPSC的潜在异质性将通过单细胞RNA序列分析来鉴定， 生物信息学分析这一提案的完成对增进我们的知识具有突出的潜力 内源性DPSC在磨牙中的基础，导致组织再生治疗的新策略。