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: 10366016
• 负责人: Takamitsu Maruyama
• 金额: $ 24.88万
• 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 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10366016
• 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和表征 抽象的 该建议的目的是识别和表征成人内源性牙髓干细胞（DPSC） 小鼠磨牙。尽管不断生长的小鼠切牙已被用作模型系统 牙齿中的内源性DPSC表征了牙齿干细胞，磨牙仍研究了研究。与门牙不同， 小鼠磨牙并不是不断生长，并且类似于人类的牙齿。因此，这对于领域至关重要 干细胞生物学以及牙髓再生疗法，以识别和表征内源性DPSC 从磨牙中分离出来。为了进行这项研究，我们开发了一个小鼠模型，其中axin2+牙齿 磨牙中的纸浆细胞被遗传标记。我们的初步评估表明AXIN2+ DPSC是 能够自我更新并区分成熟的odontoblasts在体内一年。另外， 移植的牙髓细胞能够再生纸浆样组织。最初的发现显示了一个区别 在从其他成年干细胞和DPSC中再生的组织类型中，表明它们独特的细胞 内源性DPSC中存在可塑性。在此应用程序中，我们将测试表达AXIN2的DPSC是否可以满足 成年干细胞的标准。我们还将在单个细胞水平上检查干细胞性质。这 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序列分析和 生物信息学分析。该提案的完成具有提高我们知识的杰出潜力 内源性DPSC的基础，导致组织再生疗法的新型策略。