A Novel Large Animal Model for Studying the Developmental Potential and Function of LGR5 Stem Cells in Vivo and in Vitro
用于研究 LGR5 干细胞体内外发育潜力和功能的新型大型动物模型
基本信息
- 批准号:10575566
- 负责人:
- 金额:$ 19万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-01-01 至 2024-11-30
- 项目状态:已结题
- 来源:
- 关键词:AblationAddressAllelesAnatomyAnimal ModelBasic ScienceBleomycinCell LineageCellsClinicalClustered Regularly Interspaced Short Palindromic RepeatsCochleaComplexDataDevelopmentDiseaseDoseFamily suidaeFetal LungFutureGene ExpressionGenerationsGenesGenetic TranscriptionGuidelinesHair follicle structureHealthHomeostasisHumanIn VitroInjuryKidneyLGR5 geneLOX geneLabelLiverLungMaintenanceMalignant NeoplasmsModelingMolecularMorphogenesisMusNatural regenerationOralOrganOrganoidsPathologicPerformancePhenotypePhysiologicalPhysiologyPlayPopulationPreparationProcessRegenerative capacityRegenerative researchRegulationReporterResearchResolutionRoleSeminalSkinSpatial DistributionStudy modelsSystemTamoxifenTissuesTracerTransgenesTransgenic OrganismsTranslatingTransplantationValidationadult stem cellbody systemdesigndosagefetal stem cellgastrointestinal systemhuman diseaseimprovedin vivoinjury and repairinterestlung injurynovelpromoterresponsesomatic cell nuclear transferstem cellstherapy developmenttissue repairtool
项目摘要
Project Summary
LGR5, a marker of adult and fetal stem cells in various tissues and organs, has been studied extensively for the
past decades. Cells expressing LGR5 play key roles in organ/tissue development, homeostasis, regeneration,
and disease, including cancer. Therefore, having the ability to identify, track, and manipulate these cells in vitro
and in vivo, will allow their detailed role in normal and pathological organ function. To date, most of the research
on LGR5 cells has been performed using mice, which have significant anatomical, physiological, and molecular
differences from the human. Utilizing a newly developed LGR5-H2B-GFP pig line we have demonstrated its wide
utility for studying the role of these unique cells and have now made seminal observations in a variety of
tissues/organs. However, we have also been unable to address some key aspects due to the inability of the
existing model to analyze the differentiated progeny (lineage tracking) of LGR5 cells during development, after
transplantation, or during the process of injury and repair. In addition, while we have been able to inactivate both
alleles of the LGR5 gene, we do not have the ability to delete the cell itself. Being able to delete the LGR5
expressing cell will increase our understanding of the importance of this unique cell (versus the LGR5 gene itself)
in the phenotypes of interest. Thus, to overcome these two deficiencies, and further increase the value and
impact of the original LGR5-H2B-GFP animal model, we propose to develop a highly improved LGR5 pig line
that will allow labeling of the LGR5 cell, tracking of its progeny after injury, and delete it when desired. The high
concordance between human and pig results to date with respect to LGR5 expression and function, not only
increases the value of this line for basic research, but also for rapidly translating clinical findings to humans,
further increasing the impact of this unique animal model. Successful completion of the proposed aims will
generate a powerful animal model for study of translational aspects of LGR5 stem cells of the gut, lung, skin,
liver, cochlea, and kidney among others.
项目摘要
LGR 5是各种组织和器官中成人和胎儿干细胞的标志物,已经被广泛研究用于治疗肿瘤。
过去几十年表达LGR 5的细胞在器官/组织发育、稳态、再生
疾病,包括癌症。因此,有能力在体外识别,跟踪和操纵这些细胞,
在体内,将允许它们在正常和病理器官功能中的详细作用。到目前为止,大多数研究
已经使用小鼠对LGR 5细胞进行了研究,这些小鼠具有显著的解剖学、生理学和分子生物学特征。
与人类的差异。利用新开发的LGR 5-H2 B-GFP猪系,我们已经证明了其广泛的
研究这些独特细胞的作用,现在已经在各种各样的细胞中进行了开创性的观察。
组织/器官。然而,由于联合国无法解决一些关键问题,
现有的模型来分析LGR 5细胞在发育过程中的分化后代(谱系追踪),
移植或在损伤和修复过程中。此外,虽然我们已经能够同时
LGR 5基因的等位基因,我们没有能力删除细胞本身。能够删除LGR 5
表达细胞将增加我们对这种独特细胞(相对于LGR 5基因本身)重要性的理解
在感兴趣的表型中。因此,要克服这两个不足,进一步提高价值,
LGR 5-H2 B-GFP动物模型的影响,我们提出开发一个高度改进的LGR 5猪系
这将允许标记LGR 5细胞,在损伤后追踪其后代,并在需要时将其删除。高
迄今为止,人类和猪的结果在LGR 5表达和功能方面的一致性,不仅
增加了这条线在基础研究中的价值,也增加了将临床发现快速转化为人类的价值,
进一步增加了这种独特的动物模型的影响。成功实现拟议目标将
产生一个强大的动物模型,用于研究肠道,肺,皮肤,
肝脏耳蜗和肾脏等
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Jorge A Piedrahita其他文献
Jorge A Piedrahita的其他文献
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{{ truncateString('Jorge A Piedrahita', 18)}}的其他基金
A large animal model to elucidate the role of LGR5 stem cells in cancer
阐明 LGR5 干细胞在癌症中作用的大型动物模型
- 批准号:
10337272 - 财政年份:2021
- 资助金额:
$ 19万 - 项目类别:
U-TEAM: Undergraduate Interdisciplinary Training in Comparative Biomedical Research
U-TEAM:比较生物医学研究本科跨学科培训
- 批准号:
10158531 - 财政年份:2019
- 资助金额:
$ 19万 - 项目类别:
U-TEAM: Undergraduate Interdisciplinary Training in Comparative Biomedical Research
U-TEAM:比较生物医学研究本科跨学科培训
- 批准号:
10407047 - 财政年份:2019
- 资助金额:
$ 19万 - 项目类别:
U-TEAM: Undergraduate Interdisciplinary Training in Comparative Biomedical Research
U-TEAM:比较生物医学研究本科跨学科培训
- 批准号:
10627913 - 财政年份:2019
- 资助金额:
$ 19万 - 项目类别:
Immunodeficient Pigs for Stem Cell-Based Regenerative Medicine
用于干细胞再生医学的免疫缺陷猪
- 批准号:
9766880 - 财政年份:2017
- 资助金额:
$ 19万 - 项目类别:
Immunodeficient Pigs for Stem Cell-Based Regenerative Medicine
用于干细胞再生医学的免疫缺陷猪
- 批准号:
9384776 - 财政年份:2017
- 资助金额:
$ 19万 - 项目类别:
Improved large animal model for the study of adult stem cells
用于成体干细胞研究的改进大型动物模型
- 批准号:
8771569 - 财政年份:2014
- 资助金额:
$ 19万 - 项目类别:
Swine in Biomedical Research Conference 2014, Challenges and Opportunities
2014 年猪生物医学研究会议,挑战与机遇
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8710842 - 财政年份:2014
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$ 19万 - 项目类别:
Maximizing the utilization of porcine animal models by development of a pygmy pig
通过开发侏儒猪最大限度地利用猪动物模型
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8449028 - 财政年份:2012
- 资助金额:
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Maximizing the utilization of porcine animal models by development of a pygmy pig
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8300610 - 财政年份:2012
- 资助金额:
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