Mechanical Control of Mesenchymal-to-Epithelial Transition
间充质到上皮转变的机械控制
基本信息
- 批准号:9336427
- 负责人:
- 金额:$ 54.96万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2016
- 资助国家:美国
- 起止时间:2016-09-15 至 2018-08-31
- 项目状态:已结题
- 来源:
- 关键词:ApicalBehaviorBilateralBiologicalBiological ModelsBiological ProcessBiomechanicsBiophysical ProcessCell AdhesionCellsCellular StructuresCellular biologyCerealsChemicalsComplexCuesDataDevelopmentDiagnostic testsDiseaseEmbryoEmbryonic DevelopmentEnvironmentEpithelialEpitheliumEventExperimental ModelsFibrosisGene ExpressionGenesGenomicsGoalsHeartHourIn VitroLifeLocationMalignant NeoplasmsMapsMechanical StressMechanicsMesenchymalMicroscopicMicroscopyModelingMolecularMonitorMovementNatural regenerationNeoplasm MetastasisOrganOrganogenesisPathway AnalysisPathway interactionsPhenotypePlayPopulationProcessProteinsRanaRegulationResearchResearch PersonnelRoleShapesStem cellsStudy modelsSurfaceSystemTestingTherapeuticTissuesTractionUniversitiesWound HealingXenopus laevisbasebiophysical techniquescardiogenesiscell motilitycell typeembryo cellepithelial to mesenchymal transitiongenetic analysisheart primordiumin vivoin vivo Modelinsightintravital imagingmigrationprecursor cellprogenitorprogramsself assemblysuccesstemporal measurementthree-dimensional modelingtooltranscriptome
项目摘要
Project Summary:
Mesenchymal-to-epithelial transitions (METs) play fundamental roles in many tissue-shaping
processes including embryonic development, fibrosis, and stem cell reprogramming, yet we know little about
the biomechanical cues that initiate and regulate METs, what pathways are regulated by METs, and how newly
epithelialized clusters grow in size. In this project we seek to define the biophysical and biomechanical
principles that guide MET in vivo during early development of the heart and ex vivo within 3D mesenchymal
aggregates. During heart development, in vivo METs occur as bilateral populations of heart progenitor cells
migrate toward the ventral midline. We have developed one experimental model system in which METs shape
the early heart primordia in Xenopus laevis and another where METs occur spontaneously in ex vivo 3D
aggregates of X. laevis embryonic mesenchymal cells. These models are compatible with live microscopy and
are uniquely accessible to combined biophysical, biomechanical, cell biological, and genetic analysis. Using
these models, studies in our lab have revealed a complex interplay between cell and tissue biomechanics and
MET both in vivo and ex vivo. Intra vital imaging of heart precursor cells reveals that they change their
mechanical mode of migration as they undergo MET. Our lab has also found that METs in both models are
highly sensitive to tissue tension and cell contractility. In our first aim we focus on describing phenotypic
changes in heart progenitor cells as they undergo MET and how MET alters their mechanics and migration
through a cell dense microenvironment. Our second aim seeks to identify mechanical and molecular pathways
that drive MET in 3D mesenchymal aggregates, focusing on pathways that transduce mechanical cues in this
process. In our third aim, we explore the cell biology of MET initiation and spreading in 3D aggregates and test
our findings within a 3D ex vivo model of heart formation. We focus our studies on in vivo and ex vivo models
of MET to identify and test the role of mechanical cues in MET during heart formation and how biomechanical
and biophysical processes integrate with the cell biological processes that drive tissue assembly. Due to the
similarities of developmental METs with METs in other systems, our findings will likely expose common
pathways regulating METs during regeneration, wound healing, fibrosis, and cancers metastases.
项目总结:
间充质-上皮间充质转化(METS)在许多组织塑造中起着基础性作用
包括胚胎发育、纤维化和干细胞重编程等过程,但我们对此知之甚少
启动和调节蛋氨酸的生物力学线索,甲硫氨酸调节的途径是什么,以及新的
上皮化团的大小逐渐增大。在这个项目中,我们试图定义生物物理和生物力学
指导心脏早期发育的体内和体外3D间充质内MET的原则
集合体。在心脏发育过程中,体内的蛋氨酸以双侧心脏前体细胞群的形式出现
向腹中线移动。我们开发了一个实验模型系统,在这个系统中,Mets形成了
非洲爪哇和另一种甲硫氨酸在体外3D中自发发生的早期心脏原基
莱氏X.laevis胚胎间充质细胞聚集体。这些模型与活显微镜兼容,并且
是唯一可用于生物物理、生物力学、细胞生物学和遗传分析的组合。vbl.使用
这些模型,我们实验室的研究揭示了细胞和组织生物力学和
在体内和体外都相遇。心脏前体细胞的活体成像显示,它们改变了它们的
它们在经历相遇时的机械迁移方式。我们的实验室还发现,两种模型中的Met都是
对组织张力和细胞收缩高度敏感。在我们的第一个目标中,我们专注于描述表型
心脏祖细胞在经历MET时的变化以及MET如何改变其机制和迁移
通过细胞密集的微环境。我们的第二个目标是找出机械和分子途径
这种驱动力在3D间充质聚集体中相遇,专注于在这一过程中传递机械线索的途径
进程。在我们的第三个目标中,我们探索了MET在3D聚集体中的启动和扩散的细胞生物学并进行了测试
我们在心脏形成的3D体外模型中的发现。我们专注于体内和体外模型的研究。
在心脏形成过程中识别和测试机械信号在MET中的作用以及生物力学如何
生物物理过程与驱动组织组装的细胞生物过程相结合。由于
发育中的蛋氨酸与其他系统中的蛋氨酸的相似性,我们的发现可能会揭示共同的
在再生、伤口愈合、纤维化和癌症转移过程中调节蛋氨酸的途径。
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)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
LANCE A. DAVIDSON其他文献
LANCE A. DAVIDSON的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('LANCE A. DAVIDSON', 18)}}的其他基金
US National Symposium on Frontiers in Biomechanics: Mechanics of Development
美国国家生物力学前沿研讨会:发展力学
- 批准号:
8204038 - 财政年份:2011
- 资助金额:
$ 54.96万 - 项目类别:
Biophysics of development buffering: Temperature as a tool to study how the cytos
发育缓冲的生物物理学:温度作为研究细胞如何发育的工具
- 批准号:
7976887 - 财政年份:2010
- 资助金额:
$ 54.96万 - 项目类别:
Biophysics of development buffering: Temperature as a tool to study how the cytos
发育缓冲的生物物理学:温度作为研究细胞如何发育的工具
- 批准号:
8106442 - 财政年份:2010
- 资助金额:
$ 54.96万 - 项目类别:
相似国自然基金
greenwashing behavior in China:Basedon an integrated view of reconfiguration of environmental authority and decoupling logic
- 批准号:
- 批准年份:2024
- 资助金额:万元
- 项目类别:外国学者研究基金项目
相似海外基金
Understanding the interplay between the gut microbiome, behavior and urbanisation in wild birds
了解野生鸟类肠道微生物组、行为和城市化之间的相互作用
- 批准号:
2876993 - 财政年份:2027
- 资助金额:
$ 54.96万 - 项目类别:
Studentship
Collaborative Research: Chain Transform Fault: Understanding the dynamic behavior of a slow-slipping oceanic transform system
合作研究:链变换断层:了解慢滑海洋变换系统的动态行为
- 批准号:
2318855 - 财政年份:2024
- 资助金额:
$ 54.96万 - 项目类别:
Continuing Grant
Collaborative Research: Subduction Megathrust Rheology: The Combined Roles of On- and Off-Fault Processes in Controlling Fault Slip Behavior
合作研究:俯冲巨型逆断层流变学:断层上和断层外过程在控制断层滑动行为中的综合作用
- 批准号:
2319848 - 财政年份:2024
- 资助金额:
$ 54.96万 - 项目类别:
Standard Grant
Collaborative Research: Subduction Megathrust Rheology: The Combined Roles of On- and Off-Fault Processes in Controlling Fault Slip Behavior
合作研究:俯冲巨型逆断层流变学:断层上和断层外过程在控制断层滑动行为中的综合作用
- 批准号:
2319849 - 财政年份:2024
- 资助金额:
$ 54.96万 - 项目类别:
Standard Grant
MCA Pilot PUI: From glomeruli to pollination: vertical integration of neural encoding through ecologically-relevant behavior
MCA Pilot PUI:从肾小球到授粉:通过生态相关行为进行神经编码的垂直整合
- 批准号:
2322310 - 财政年份:2024
- 资助金额:
$ 54.96万 - 项目类别:
Continuing Grant
CAREER: A cortex-basal forebrain loop enabling task-specific cognitive behavior
职业:皮层基底前脑环路实现特定任务的认知行为
- 批准号:
2337351 - 财政年份:2024
- 资助金额:
$ 54.96万 - 项目类别:
Continuing Grant
Conference: 2024 Photosensory Receptors and Signal Transduction GRC/GRS: Light-Dependent Molecular Mechanism, Cellular Response and Organismal Behavior
会议:2024光敏受体和信号转导GRC/GRS:光依赖性分子机制、细胞反应和生物体行为
- 批准号:
2402252 - 财政年份:2024
- 资助金额:
$ 54.96万 - 项目类别:
Standard Grant
Nanoscopic elucidation of dynamic behavior of RNA viral nucleocapsid proteins using high-speed atomic force microscopy (HS-AFM)
使用高速原子力显微镜 (HS-AFM) 纳米级阐明 RNA 病毒核衣壳蛋白的动态行为
- 批准号:
24K18449 - 财政年份:2024
- 资助金额:
$ 54.96万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
ERI: Data-Driven Analysis and Dynamic Modeling of Residential Power Demand Behavior: Using Long-Term Real-World Data from Rural Electric Systems
ERI:住宅电力需求行为的数据驱动分析和动态建模:使用农村电力系统的长期真实数据
- 批准号:
2301411 - 财政年份:2024
- 资助金额:
$ 54.96万 - 项目类别:
Standard Grant
Understanding the synthesis and electronic behavior of beta tungsten thin film materials
了解β钨薄膜材料的合成和电子行为
- 批准号:
23K20274 - 财政年份:2024
- 资助金额:
$ 54.96万 - 项目类别:
Grant-in-Aid for Scientific Research (B)