The role of mitochondrial regulation in cell lineage specification and function
线粒体调节在细胞谱系规范和功能中的作用
基本信息
- 批准号:10501649
- 负责人:
- 金额:$ 42.63万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-09-01 至 2027-06-30
- 项目状态:未结题
- 来源:
- 关键词:BioenergeticsBiogenesisBiologyCell Differentiation processCell LineageCell SurvivalCell modelCell physiologyCellsClustered Regularly Interspaced Short Palindromic RepeatsCuesDefectDevelopmentDiseaseEnvironmentEpigenetic ProcessEukaryotic CellEventExcisionFunctional disorderGeneticGenetic TranscriptionInstructionMaintenanceMalignant NeoplasmsMediatingMetabolicMetabolismMitochondriaModificationMorphologyOrgan Culture TechniquesOrganellesPathogenesisPharmacologyPhysiologyProcessPublishingRegulationResearchRoleSignal TransductionSystemTherapeuticWorkhigh resolution imagingmitochondrial metabolismpublic health relevancestem cellstooltrafficking
项目摘要
ABSTRACT
The role of mitochondrial regulation in cell lineage specification and function
During cell lineage specification, metabolic reprogramming, together with transcriptional and epigenetic
modifications in the progenitor cells are integral parts of cellular adaptations to the cell fate instructive cues.
When this process goes awry, developmental defects as well as malignancies will occur. Common in all the
cellular systems, mitochondria are bioenergetic, biosynthetic and signaling organelles central to metabolic
remodeling. Understanding mechanisms of mitochondrial function during lineage specification will be critical for
therapeutic normalization of derailed cellular metabolism and functions in pathogenesis. Though mitochondrial
regulation is still unclear, our published and preliminary work revealed critical roles of mitochondrial
metabolism and mitochondrial dynamics during cell lineage specification. Furthermore, differentiated cells
continue to receive low-level, constitutive signaling in the basal state (“tonic signals”), important for cell survival
or functions. Our research suggested that mitochondrial regulation is actively maintained in mature
differentiated cells downstream of tonic signals and revealed potential new regulators for this process. The
overarching theme of our research is to unravel the diverse mitochondria mediated mechanisms regulating cell
lineage differentiation and homeostatic functions. In Project 1, we will use high resolution imaging to
characterize distinct mitochondrial morphology, and dynamic events in live cells. Using genetic tools, and an
organ culture system to model cell lineage specification, we will decipher the role of mitochondrial dynamics in
metabolic remodeling during differentiation. In Project 2, using a sophisticated system of transferring cells into
environments with defined levels of tonic signals, we will assess the alterations in mitochondrial dynamics and
functions in the presence and absence of tonic signals. Through pharmacological means or genetic
modifications such as CRISPR/Ca9 in differentiated cells, we will determine the causal relationship between
mitochondrial regulation and maintenance of cellular functions. Upon completion of our work, we will have
uncovered the versatile mechanisms by which mitochondria influence lineage specification and homeostatic
functions.
摘要
线粒体调控在细胞谱系规范和功能中的作用
在细胞谱系指定期间,代谢重新编程以及转录和表观遗传
祖细胞的修饰是细胞适应细胞命运的不可或缺的部分,这是指导性线索。
当这一过程出错时,就会出现发育缺陷和恶性肿瘤。共同存在于所有
细胞系统,线粒体是代谢中心的生物能量、生物合成和信号传递细胞器。
改建。了解线粒体在谱系确定过程中的功能机制将对
在发病机制中细胞代谢和功能脱轨的治疗正常化。虽然线粒体
调控机制尚不清楚,我们已发表的初步工作揭示了线粒体的关键作用
细胞谱系确定过程中的代谢和线粒体动力学。此外,分化的细胞
在基础状态下继续接受低水平的结构性信号(“紧张性信号”),这对细胞存活很重要
或功能。我们的研究表明,线粒体的调节在成熟期保持活跃。
紧张性信号下游的分化细胞,并揭示了这一过程的潜在新调节因子。这个
我们研究的主要主题是解开线粒体调节细胞的不同机制
血统分化和内环境平衡功能。在项目1中,我们将使用高分辨率成像来
描述活细胞中不同的线粒体形态和动态事件。使用基因工具,以及一个
器官培养系统来模拟细胞谱系规范,我们将破译线粒体动力学在
分化过程中的代谢重塑。在项目2中,使用一个复杂的系统将细胞转移到
在具有特定紧张性信号水平的环境中,我们将评估线粒体动力学和
在主音信号存在和不存在的情况下起作用。通过药物手段或基因
CRISPR/Ca9等修饰在分化细胞中的作用,我们将确定两者之间的因果关系
线粒体调节和维持细胞功能。在我们的工作完成后,我们将拥有
揭示了线粒体影响谱系规范和动态平衡的多种机制
功能。
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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Meng Zhao其他文献
Meng Zhao的其他文献
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{{ truncateString('Meng Zhao', 18)}}的其他基金
Investigating Isthmin as an adipose-to-muscle messenger that promotes muscle protein synthesis
研究 Isthmin 作为促进肌肉蛋白质合成的脂肪到肌肉信使
- 批准号:
10664500 - 财政年份:2023
- 资助金额:
$ 42.63万 - 项目类别:
The role of mitochondrial regulation in cell lineage specification and function
线粒体调节在细胞谱系规范和功能中的作用
- 批准号:
10798885 - 财政年份:2022
- 资助金额:
$ 42.63万 - 项目类别:
The role of mitochondrial regulation in cell lineage specification and function
线粒体调节在细胞谱系规范和功能中的作用
- 批准号:
10818978 - 财政年份:2022
- 资助金额:
$ 42.63万 - 项目类别:
Role of purinergic receptor P2X7 in the differentiation and function of iNKT cell subsets
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- 批准号:
10339355 - 财政年份:2021
- 资助金额:
$ 42.63万 - 项目类别:
Role of purinergic receptor P2X7 in the differentiation and function of iNKT cell subsets
嘌呤能受体P2X7在iNKT细胞亚群分化和功能中的作用
- 批准号:
10090983 - 财政年份:2021
- 资助金额:
$ 42.63万 - 项目类别:
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Mitochondria are double-membrane-bound organelles that are essential for cellular energy production. A fundamental question in eukaryotic cell biology is how the biogenesis of mitochondria is achieved and regulated
线粒体是双膜结合的细胞器,对于细胞能量生产至关重要。
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