Novel mechanisms of vasculogenesis
血管发生的新机制
基本信息
- 批准号:10418662
- 负责人:
- 金额:$ 51.53万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-06-05 至 2025-05-31
- 项目状态:未结题
- 来源:
- 关键词:AblationAtherosclerosisBiological ModelsBlood CirculationBlood VesselsCellsDataDefectDevelopmentDiabetes MellitusDyslipidemiasEmbryoEmbryonic DevelopmentEndothelial CellsEndotheliumFluoresceinGenesGeneticGenetic RecombinationGrowthHematopoieticHumanHypertensionImageImmunohistochemistryKnowledgeLeadMammalsMethodsMolecularMolecular AnalysisMusNatural regenerationOrganPhenotypePlayPopulationPronephric structureRecoveryReporterRoleSignal PathwaySiteSourceTestingTherapeuticTimeTissuesTransgenic OrganismsVascular DiseasesVascular Endothelial CellVascular Endothelial Growth FactorsVascular EndotheliumVascular regenerationVenousVenusVertebratesZebrafishangiogenesisbasedefined contributionin vivoinjury and repairintercalationjunctional adhesion moleculemonolayermutantnovelnovel therapeutic interventionprogenitorrepairedstem cellstherapeutically effectivetranscription factorvascular contributionsvascular endothelial dysfunctionvasculogenesis
项目摘要
Project Summary
Multiple vascular diseases including hypertension, diabetes, atherosclerosis, and others are associated
with the dysfunction of vascular endothelium. However, there are currently no effective methods to incorporate
new endothelial cells into damaged vessels in vivo which could contribute to vascular regeneration and repair.
New blood vessels form by two distinct mechanisms, vasculogenesis, which is differentiation of
vascular endothelial cells de novo, and angiogenesis, formation of new vessels by branching from the existing
vessels. It is currently thought that vasculogenesis is largely limited to the initial vascular network during
embryogenesis, while the majority of the later vessels form by angiogenesis from the existing vasculature.
While it is difficult to study vasculogenesis in the mammalian embryos, zebrafish has emerged as an
advantageous model system to study vascular development. Molecular mechanisms that control vascular
development are highly conserved between all vertebrates including zebrafish and humans.
Here we have discovered a novel population of putative vascular progenitors in the zebrafish embryos.
These cells show high expression of ETS transcription factor etv2, a known key regulator of vasculogenesis,
and are located adjacent to the pronephros (pronephros-associated cells, PACs). Our preliminary data indicate
that PACs are the major source of organ specific vasculature, and they contribute to the embryonic vasculature
by a novel mechanism of cell intercalation into functional blood vessels. Our data further suggest that PACs
are likely conserved in mammalian embryos. In addition, we have identified Junctional Adhesion Molecule
Jam2b as one of key regulators required for PAC formation. We hypothesize that PACs are a novel group of
multipotent vascular progenitors which provide important contribution for vascular growth.
The following specific aims are proposed: 1) Define contribution of PACs to different types of blood
vessels; 2) Identify functional role for PACs in vascular development; 3) Identify the role of Jam2b and other
upstream regulators in the formation of PACs and vascular development. Lineage tracing approaches will be
employed to determine contribution of PACs to different types of vessels in zebrafish embryos. PAC ablation
and etv2 conditional inhibition strategies will be used to test the functional role of PACs in zebrafish, and their
formation will also be investigated in murine embryos. The role of jam2b in PAC formation, its interaction with
Vegf signaling pathway, and functional roles of other PAC-enriched genes will be analyzed in zebrafish.
Data obtained in this proposal will answer the key questions regarding the identity and functional role of
PACs, and are likely to uncover a novel mechanism of vascular growth. The mechanisms of vasculogenesis
are highly conserved, and our preliminary data suggest that similar progenitors are also present in the
mammalian embryos. Understanding the mechanism of how PACs form and incorporate into existing
vasculature may lead to a new direction to repair damaged vessels for therapeutic purposes.
项目总结
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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Saulius Sumanas其他文献
Saulius Sumanas的其他文献
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{{ truncateString('Saulius Sumanas', 18)}}的其他基金
Role of SHE and ABL signaling in vascular tubulogenesis
SHE 和 ABL 信号在血管生成中的作用
- 批准号:
10587279 - 财政年份:2023
- 资助金额:
$ 51.53万 - 项目类别:
The role of Collagen COL22A1 in intracranial aneurysms and vascular stability
胶原蛋白 COL22A1 在颅内动脉瘤和血管稳定性中的作用
- 批准号:
9926909 - 财政年份:2017
- 资助金额:
$ 51.53万 - 项目类别:
The role of Collagen COL22A1 in intracranial aneurysms and vascular stability
胶原蛋白 COL22A1 在颅内动脉瘤和血管稳定性中的作用
- 批准号:
9381376 - 财政年份:2017
- 资助金额:
$ 51.53万 - 项目类别:
THE ROLE OF COLLAGEN COL22A1 IN INTRACRANIAL ANEURYSMS AND VASCULAR STABILITY
胶原蛋白 COL22A1 在颅内动脉瘤和血管稳定性中的作用
- 批准号:
10212566 - 财政年份:2017
- 资助金额:
$ 51.53万 - 项目类别:
Molecular Mechanisms of Arterial-Venous Differentiation in Zebrafish
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- 批准号:
8083384 - 财政年份:2011
- 资助金额:
$ 51.53万 - 项目类别:
Molecular Mechanisms of Arterial-Venous Differentiation
动静脉分化的分子机制
- 批准号:
8645705 - 财政年份:2011
- 资助金额:
$ 51.53万 - 项目类别:
Molecular Mechanisms of Arterial-Venous Differentiation
动静脉分化的分子机制
- 批准号:
8449174 - 财政年份:2011
- 资助金额:
$ 51.53万 - 项目类别:
Molecular Mechanisms of Arterial-Venous Differentiation
动静脉分化的分子机制
- 批准号:
8247717 - 财政年份:2011
- 资助金额:
$ 51.53万 - 项目类别:
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