Identifying niche factors regulating distinct properties of AT2 stem cells
识别调节 AT2 干细胞独特特性的生态位因子
基本信息
- 批准号:9767857
- 负责人:
- 金额:$ 54.39万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2018
- 资助国家:美国
- 起止时间:2018-08-22 至 2022-05-31
- 项目状态:已结题
- 来源:
- 关键词:3-DimensionalAblationAcuteAdult Respiratory Distress SyndromeAgingAlveolarAutomobile DrivingBindingBiochemistryBronchoscopyCell DeathCell ProliferationCell TransplantationCell TransplantsCell divisionCellsChronicChronic Obstructive Airway DiseaseCuesDataDiagnosisDiseaseDisease ProgressionEGF geneElderlyEnvironmentEpidermal Growth Factor ReceptorEpithelialEpithelial CellsFailureFibroblastsFosteringFunctional disorderGasesGoalsGrowthHumanImmuneInjuryIntegrinsKnowledgeLeadLearningLifeLigandsLongevityLungLung CapacityLung diseasesMaintenanceMapsMedicalMinorMitogensModelingMolecularMorbidity - disease rateMusNatural regenerationOrganParacrine CommunicationPathologyPatientsPharmacologyPneumoniaPopulationProductionProliferatingPropertyRNARegulationResearchResolutionRespiratory FailureRespiratory physiologyRoleSignal PathwaySignal TransductionSignaling MoleculeSiteSmokingStem cellsSurfaceTestingTherapeuticTimeTissuesTransplantationWNT Signaling PathwayWorkalveolar type II cellautocrinebasecell behaviorcell injurydimeridiopathic pulmonary fibrosisimprovedin vivoinjuredlung injurylung regenerationmortalitynew technologynovelparacrinepreventprogramsreceptorreconstitutionrepairedresilienceresponseresponse to injurysingle cell analysissingle cell technologystem cell biologytherapeutic development
项目摘要
PROJECT SUMMARY
A number of serious respiratory diseases cause problems with gas exchange, which is the principal function of
the lungs. Some of these are sudden in onset, like lung injury from a severe pneumonia, while others develop
over long periods of time, like COPD and Idiopathic Pulmonary Fibrosis (IPF). There is some evidence that the
chronic forms of respiratory failure result from loss of the capacity of the lungs to maintain themselves, in part
due to dysfunction of resident lung stem cells that normally perform this role. Therefore, discovering the
specific molecular and cellular mechanisms by which lung stem cells are regulated throughout life may be
helpful for understanding how COPD and IPF develop. Achieving this deep level of understanding about lung
stem cell regulation may lead to improved strategies to predict, diagnose, and even pharmacologically treat
such diseases. Furthermore, given the easy accessibility of the lung via medical bronchoscopy, it is an ideal
organ to target with the delivery of healthy stem cells that might prevent disease progression or even produce
improvement if they can be successfully transplanted into diseased lungs. We have found that one of the
functional cells in the gas exchange region, the alveolar type II (AT2) cell, acts as a stem cell for mouse lung
throughout the lifespan, and identified several factors that regulate its activity. The AIMS of this proposal are to
expand our understanding of how these stem cells are regulated by studying the local environment that
provides the signals that control their activity, including proliferation and differentiation. We will investigate
three specific and distinct aspects of the stem cell behavior, including how it is induced to proliferate to
generate new cells, how it attains the capacity to transiently regulate itself in response to injury, and whether
the regulatory environment is as or more important than the stem cell itself for maintaining the lungs over the
lifespan. Our findings will significantly deepen our understanding of precisely how these lung stem cells can be
deliberately manipulated to generate large numbers suitable for cell transplantation, or by pharmacologically
driving their activity for therapeutic 're-growth' purposes.
项目摘要
许多严重的呼吸道疾病引起气体交换问题,而气体交换是呼吸系统的主要功能。
肺其中一些是突然发作的,如严重肺炎造成的肺损伤,而另一些则是发展中国家的疾病。
慢性阻塞性肺疾病(COPD)和特发性肺纤维化(IPF)。有证据表明,
慢性形式的呼吸衰竭部分是由于肺丧失了维持自身的能力,
这是由于通常发挥这一作用的常驻肺干细胞的功能障碍。因此,发现
在整个生命过程中调节肺干细胞的特定分子和细胞机制可能
有助于了解COPD和IPF的发展过程。对肺有了更深层次的了解
干细胞调控可能会导致预测、诊断甚至是治疗的策略得到改进
这样的疾病。此外,考虑到通过医学支气管镜检查容易接近肺部,
通过输送健康的干细胞来靶向器官,这些干细胞可能会阻止疾病进展,甚至产生
如果它们能够成功移植到患病的肺部,就会有所改善。我们发现,
在气体交换区域的功能细胞,肺泡II型(AT 2)细胞,作为小鼠肺的干细胞
并确定了几个调节其活性的因素。本提案的目标是
通过研究当地环境,扩大我们对这些干细胞是如何调节的理解,
提供控制其活性的信号,包括增殖和分化。我们将调查
干细胞行为的三个具体和不同的方面,包括它是如何被诱导增殖,
产生新的细胞,它如何获得对损伤做出反应的瞬时调节自身的能力,以及是否
调节环境与干细胞本身一样重要,甚至更重要,以维持肺超过
寿命我们的研究结果将大大加深我们对这些肺干细胞是如何被
故意操纵以产生大量适合于细胞移植的细胞,或通过细胞移植,
驱动它们的活性用于治疗性“再生长”目的。
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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Tushar Jasubhai DESAI其他文献
Tushar Jasubhai DESAI的其他文献
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{{ truncateString('Tushar Jasubhai DESAI', 18)}}的其他基金
Cellular and molecular mechanisms of alveolar repair
肺泡修复的细胞和分子机制
- 批准号:
10750085 - 财政年份:2023
- 资助金额:
$ 54.39万 - 项目类别:
Identifying niche factors regulating distinct properties of AT2 stem cells
识别调节 AT2 干细胞独特特性的生态位因子
- 批准号:
9576667 - 财政年份:2018
- 资助金额:
$ 54.39万 - 项目类别:
Identifying niche factors regulating distinct properties of AT2 stem cells
识别调节 AT2 干细胞独特特性的生态位因子
- 批准号:
10178079 - 财政年份:2018
- 资助金额:
$ 54.39万 - 项目类别:
Single Cell Profiling and In Vivo Cellular Interrogation of Alveolar Stem Cells
肺泡干细胞的单细胞分析和体内细胞分析
- 批准号:
9130386 - 财政年份:2015
- 资助金额:
$ 54.39万 - 项目类别:
Development and maintenance of the alveolar type 1 cell
肺泡 1 型细胞的发育和维持
- 批准号:
7386391 - 财政年份:2008
- 资助金额:
$ 54.39万 - 项目类别:
Development and maintenance of the alveolar type 1 cell
肺泡 1 型细胞的发育和维持
- 批准号:
7552017 - 财政年份:2008
- 资助金额:
$ 54.39万 - 项目类别:
Development and maintenance of the alveolar type 1 cell
肺泡 1 型细胞的发育和维持
- 批准号:
7754452 - 财政年份:2008
- 资助金额:
$ 54.39万 - 项目类别:
Development and maintenance of the alveolar type 1 cell
肺泡 1 型细胞的发育和维持
- 批准号:
8207255 - 财政年份:2008
- 资助金额:
$ 54.39万 - 项目类别:
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