Genetic interactions and multifactorial genetics mediate myocardial regeneration
遗传相互作用和多因素遗传学介导心肌再生
基本信息
- 批准号:10820376
- 负责人:
- 金额:$ 6.12万
- 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:2021-02-11 至 2026-01-31
- 项目状态:未结题
- 来源:
- 关键词:AblationAddressAdultAffectAnimal ModelBeliefBirthCandidate Disease GeneCardiac MyocytesCardiovascular systemCell CycleCellsChromosomesClassificationClinicalCompetenceComplexCytokinesisDNA biosynthesisDataDiploidyEvaluationEye ColorFailureFrequenciesGenesGeneticGenetic EpistasisHDAC7 histone deacetylaseHeartHeart InjuriesHeightImpairmentIndividualInfarctionInjuryInterventionKnock-outKnockout MiceKnowledgeLaboratoriesMediatingMononuclearMouse StrainsMusMyocardialMyocardial InfarctionMyocardial tissueMyocardiumNatural regenerationNatureOther GeneticsOutcomePatientsPhasePhenotypePhosphotransferasesPlayPloidiesPolyploidyPostdoctoral FellowProcessProliferatingProteinsRNARecovery of FunctionRegenerative responseRoleSeminalTestingTherapeuticVariantWorkZebrafishcandidate identificationcardiac regenerationcell regenerationcombinatorialdesigngene functiongenetic approachgenome wide association studygenomic locusheart functioninnovationloss of functionnoveloverexpressionpermissivenesspostmitoticpostnatalregenerativerepairedsenescencetrait
项目摘要
PROJECT SUMMARY/ABSTRACT
Dogma in the cardiovascular field argues that the adult mammalian heart is essentially non-regenerative and
that this failure to regenerate is primarily attributed to the post-mitotic and polyploid nature of most
cardiomyocytes (CMs). Multiple pieces of evidence now support the idea that within the adult mammalian
myocardium, mononuclear diploid cardiomyocytes (MNDCMs) are a privileged subpopulation of CMs that have
avoided this proliferative senescence. This attribute confers a unique capacity to re-enter the cell cycle and
regenerate myocardial tissue. Our recent work in mice demonstrates that the frequency of MNDCMs and the
competence to regenerate one's heart are two interlinked and variable traits influenced by the complex genetic
background of an individual. In other words, contrary to longstanding beliefs, some individuals can mount a
meaningful regenerative response after an insult, such as a myocardial infarction. We then took a genome-
wide association strategy to identify the genes associated with the observed variation. From this analysis, we
identified Tnni3k as one candidate that regulates CM senescence by inhibiting cytokinesis, specifically. Here,
we identify two new candidate genes each of which has a unique effect on CM cell cycle and ploidy.
Furthermore, we hypothesize that identified genes will work cooperatively to maximize the trait effect, thus a
multifactorial approach to heart regeneration is prudent. Aim 1 will explore the first novel candidate for its
independent effect on heart function and CM cell cycle activity in both uninjured and post-infarction settings. It
will also be tested in combination with Tnni3k. Aim 2 will examine the effect of the second novel candidate on
CM ploidy, cell cycle, and heart regeneration both independently and in combination with Tnni3k. Our prior
GWAS study affirms that CM ploidy and cardiac regeneration are complex phenotypes relying on multiple
genetic loci. Here, we use genetic approaches to modulate multiple candidate genes in a single animal model
and we anticipate that this combinatorial approach will potentiate CM proliferation and cardiac regeneration.
项目总结/文摘
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
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Michaela Patterson其他文献
Michaela Patterson的其他文献
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{{ truncateString('Michaela Patterson', 18)}}的其他基金
Genetic interactions and multifactorial genetics mediate myocardial regeneration
遗传相互作用和多因素遗传学介导心肌再生
- 批准号:
10596360 - 财政年份:2021
- 资助金额:
$ 6.12万 - 项目类别:
Genetic interactions and multifactorial genetics mediate myocardial regeneration
遗传相互作用和多因素遗传学介导心肌再生
- 批准号:
10349456 - 财政年份:2021
- 资助金额:
$ 6.12万 - 项目类别:
Genetic interactions and multifactorial genetics mediate myocardial regeneration
遗传相互作用和多因素遗传学介导心肌再生
- 批准号:
10563217 - 财政年份:2021
- 资助金额:
$ 6.12万 - 项目类别:
Genetic interactions and multifactorial genetics mediate myocardial regeneration
遗传相互作用和多因素遗传学介导心肌再生
- 批准号:
10094842 - 财政年份:2021
- 资助金额:
$ 6.12万 - 项目类别:
Genetic interactions and multifactorial genetics mediate myocardial regeneration
遗传相互作用和多因素遗传学介导心肌再生
- 批准号:
10381182 - 财政年份:2021
- 资助金额:
$ 6.12万 - 项目类别:
Genetic Determinants of Adult Mouse Heart Regeneration
成年小鼠心脏再生的遗传决定因素
- 批准号:
9084262 - 财政年份:2015
- 资助金额:
$ 6.12万 - 项目类别:
Genetic Determinants of Adult Mouse Heart Regeneration
成年小鼠心脏再生的遗传决定因素
- 批准号:
8908963 - 财政年份:2015
- 资助金额:
$ 6.12万 - 项目类别:
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