Stem Cells in the Developing Heart
发育中的心脏中的干细胞
基本信息
- 批准号:8452203
- 负责人:
- 金额:$ 39.8万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2009
- 资助国家:美国
- 起止时间:2009-04-01 至 2014-03-31
- 项目状态:已结题
- 来源:
- 关键词:1,2-diacylglycerolAbbreviationsActininActinsAddressAdultAffectAgeAngiotensin IIAnteriorAntigensBiological ModelsBirthCalciumCalcium ChannelCalcium OscillationsCalcium-Sensing ReceptorsCardiacCardiac MyocytesCardiovascular DiseasesCell Differentiation processCell ProliferationCell divisionCell physiologyCellsCellular StructuresComplementConnexin 43Contractile ProteinsCoupledDataDevelopmentDifferentiation and GrowthDiglyceridesDiscriminationElementsEmbryoEmbryonic HeartEndoplasmic ReticulumEquationEventFluorescenceGap JunctionsGenerationsGoalsGrowthHeartHeart AtriumHomeostasisHumanHypertrophyITPR1 geneIn VitroInositolInsulin-Like Growth Factor ILaboratoriesLeadLifeMechanicsMediatingMesodermMethodologyMitoticMitotic spindleModelingMorphogenesisMusMuscle CellsMuscle ContractionMyocardialMyosin Heavy ChainsOrganPatternPeptidyl-Dipeptidase APhenotypePhysiologicalPopulationProcessProliferatingPropertyProteinsProto-Oncogene Protein c-kitPublished CommentRenin-Angiotensin SystemResearchRoleRyanodine Receptor Calcium Release ChannelSarcoplasmic ReticulumSchemeSpatial DistributionStagingStem cellsStretchingSystemTimeTransgenic MiceVentricularWorkWorkloadabstractingattenuationbasecalcium metabolismcell growthdesignfetalimmunocytochemistryin vivomechanical behaviormigrationmouse modelpostnatalprenatalprimitive cellprogenitorpromoterreceptorregenerativerepairedresponsetranscription factortripolyphosphateyoung adult
项目摘要
06. Project Summary/Abstract
This application raises the possibility that the myocyte compartment of the embryonic, fetal and post-natal
heart is generated by activation and lineage commitment of a pool of resident c-kit-positive cardiac progenitor
cells (CPCs) which are clustered in niches within the primitive heart. Cardiac morphogenesis may be mediated
by spontaneous calcium oscillations within CPCs which lead to cell growth and the acquisition of the myocyte
phenotype. The possibility is raised that the fate of CPCs is regulated by transient changes in intracellular
calcium which constitute the essential element of symmetric and asymmetric division of these primitive cells.
Similarly, calcium oscillations condition the differentiation of CPCs into functionally competent myocytes which
become electrically and mechanically excitable. To address these fundamental issues, two transgenic mouse
models have been developed: one in which EGFP is under the control of the c-kit-promoter (c-kit-EGFP
mouse) and the second in which EGFP expression is regulated by the cardiac specific ¿-myosin heavy chain
promoter (¿MHC-EGFP mouse). The c-kit-EGFP mouse should allow us to identify the embryonic stages at
which c-kit-positive-EGFP-positive CPCs appear in the forming heart, their anatomical distribution and
developmental changes in prenatal and postnatal life. The ¿MHC-EGFP mouse will permit us to define the
localization and spatial distribution of forming myocytes postnatally and this information will be complemented
with the data to be obtained in the c-kit-EGFP mouse. With these two models, the relationship between the
generation of myocytes and the activation, commitment and differentiation of CPCs will be established. These
studies will be integrated with the analysis of the electrophysiological, mechanical and calcium handling
properties of CPCs and linearly related cells together with their pattern of growth and differentiation. Ultimately,
the interdependence of cellular physiology and growth with calcium being the master regulatory system will be
determined. Therefore, the role that intracardiac progenitor cells have in the developing heart will be
characterized and this information may have important implications in the myocardial adaptations to ischemic
and non-ischemic damage later in life.
06.项目总结/摘要
这一应用提出了胚胎、胎儿和出生后的心肌细胞区室
通过激活和谱系定型一群常驻c-kit阳性心脏祖细胞产生心脏
细胞(CPC)聚集在原始心脏内的壁龛中。心脏形态发生可能是由
通过CPC内的自发钙振荡,导致细胞生长和肌细胞的获得,
表型提出了这样的可能性,即CPC的命运是由细胞内的瞬时变化调节的。
钙是构成这些原始细胞对称和不对称分裂的基本元素。
类似地,钙振荡调节CPC分化为功能上有能力的肌细胞,
变得电和机械可激发。为了解决这些基本问题,两个转基因小鼠
已经开发了模型:其中EGFP在c-kit启动子的控制下(c-kit-EGFP
第二种是EGFP的表达受心脏特异性肌球蛋白重链的调节
启动子(MHC-EGFP小鼠)。c-kit-EGFP小鼠应该可以让我们识别胚胎阶段,
哪些c-kit阳性-EGFP阳性CPC出现在形成的心脏中,它们的解剖学分布和
出生前和出生后的发育变化。MHC-EGFP小鼠将允许我们定义
出生后形成的心肌细胞的定位和空间分布,这些信息将得到补充
在c-kit-EGFP小鼠中获得的数据。有了这两个模型,
将建立肌细胞的产生和CPC的活化、定型和分化。这些
研究将与电生理、机械和钙处理的分析相结合
CPC和线性相关细胞的性质以及它们的生长和分化模式。最后,
细胞生理学和生长与钙的相互依赖性是主要的调节系统,
测定因此,心内祖细胞在发育中的心脏中的作用将是
这些信息可能对心肌对缺血的适应有重要意义。
和非缺血性损伤。
项目成果
期刊论文数量(3)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
SDF-1 axis and myocardial repair.
SDF-1 轴和心肌修复。
- DOI:10.1152/ajpheart.00876.2010
- 发表时间:2010
- 期刊:
- 影响因子:0
- 作者:Rota,Marcello
- 通讯作者:Rota,Marcello
Role of stem cells in cardiovascular biology.
- DOI:10.1111/j.1538-7836.2011.04363.x
- 发表时间:2011-07
- 期刊:
- 影响因子:0
- 作者:Hosoda T;Rota M;Kajstura J;Leri A;Anversa P
- 通讯作者:Anversa P
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Marcello Rota其他文献
Marcello Rota的其他文献
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{{ truncateString('Marcello Rota', 18)}}的其他基金
Myocyte Repolarization and Cardiac Dysfunction with Age
随年龄增长的心肌细胞复极化和心脏功能障碍
- 批准号:
10180825 - 财政年份:2018
- 资助金额:
$ 39.8万 - 项目类别:
Myocyte Repolarization and Cardiac Dysfunction with Age
随年龄增长的心肌细胞复极化和心脏功能障碍
- 批准号:
9920638 - 财政年份:2018
- 资助金额:
$ 39.8万 - 项目类别:
Myocyte Repolarization and Cardiac Dysfunction with Age
随年龄增长的心肌细胞复极化和心脏功能障碍
- 批准号:
10393012 - 财政年份:2018
- 资助金额:
$ 39.8万 - 项目类别:
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