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Using single cell transcriptomic analysis to uncover genetic pathways for de novo generation of dental epithelial progenitors

Using single cell transcriptomic analysis to uncover genetic pathways for de novo generation of dental epithelial progenitors
使用单细胞转录组分析揭示牙上皮祖细胞从头生成的遗传途径
批准号:
10428476
负责人:
Jimmy Kuang-Hsien Hu
金额:
$15.6万
依托单位国家:
美国
项目类别:
财政年份:
2021
资助国家:
美国
项目状态:
已结题
起止时间:
2021-06-14 至 2024-05-31

项目摘要

项目成果

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中文摘要
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英文摘要
PROJECT SUMMARY Effective utilization of organ-specific somatic stem cells to repair injured tissues or to bioengineer organs will revolutionize disease treatment and relieve numerous problems caused by aging and trauma. However, it remains significantly challenging to derive somatic stem cells with precision and expand them with high efficiency for clinical applications. The technical hurdles are in large part due to our incomplete understanding of the genetic regulation that controls fate specification of progenitors during development, as well as cell plasticity in adults. Teeth provide an excellent test case to further understand these aspects and apply clinically, as adult human teeth do not maintain dental epithelial stem cells and lack the capability to regenerate. The mouse tooth is a powerful model system to study both organogenesis and adult stem cell-based regeneration, and amenable for both in vivo genetic studies and ex vivo manipulations to investigate progenitor cell functions. Leveraging this remarkable experimental system and combining it with cutting-edge single cell transcriptomic analysis, this proposal will deliver an in depth understanding of the genetic program and transcriptional changes during the formation of dental epithelial progenitors. This knowledge will allow us to identify a genetic network and critical regulators required to specify the dental fate and provide a blueprint to derive dental progenitors by differentiating pluripotent stem cells along a genetic path. In parallel, this project will test the function and utilization of IRX1/2 and YAP in inducing the formation of dental progenitors through differentiation of oral epithelium and dedifferentiation of ameloblasts respectively. We will compare single cell transcriptomes between induced, embryonic, and adult progenitors to determine whether IRX1/2 and YAP can activate a dental genetic program. Based on these data, we will also be able to address an important question in stem cell biology, which is how different progenitor types in embryos and adults resemble each other transcriptionally. The main innovation of the project arises from the integration of genomic techniques and mouse genetic models to understand the genetic regulation of dental progenitor and stem cell formation, which is understudied. Such knowledge will form the basis of future research and grant applications, and enable developmental principle-driven approaches to tooth bioengineering.
期刊论文(3)
专著(0)
科研奖励(0)
会议论文
DOI: 10.1242/dev.200539
发表时间: 2022-08-15
期刊: Development (Cambridge, England)
影响因子: --
作者: []
通讯作者:
Nail mesenchyme: Tipping the hand on regeneration.
指甲间充质:促进再生。
DOI: 10.1016/j.celrep.2022.111960
发表时间: 2023
期刊: Cell reports
影响因子: 8.8
作者: [Hu,JimmyK]
通讯作者: Hu,JimmyK
Mechanical regulation of transcription in dental epithelial stem cells through cell packing and tissue forces
Mechanical regulation of transcription in dental epithelial stem cells through cell packing and tissue forces
An investigation of the roles of mechanical signaling in YAP-mediated tooth renew
The role of YAP/TAZ and Hippo signaling in mouse incisor stem cells
海外基金