Regulators of Development and Quiescence in the Human Muscle Stem Cell Lineage
人类肌肉干细胞谱系发育和静止的调节因子
基本信息
- 批准号:10239080
- 负责人:
- 金额:$ 60.95万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2019
- 资助国家:美国
- 起止时间:2019-09-25 至 2024-08-31
- 项目状态:已结题
- 来源:
- 关键词:AdultBasal laminaBiologicalBiological AssayBiologyCell Differentiation processCell LineageCell TherapyCell TransplantationCell physiologyCellsCharacteristicsChick EmbryoComplexDataDecision MakingDevelopmentDiseaseEmbryoExhibitsGenesGoalsHDAC1 geneHematopoietic stem cellsHeterogeneityHistone Deacetylase InhibitorHumanHuman DevelopmentImageIn VitroKnowledgeLaboratoriesLightMaintenanceMediatingMethodsMinorMolecularMusMuscleMuscle FibersMuscle satellite cellMyoblastsMyopathyNatural regenerationPAX7 genePathway interactionsPluripotent Stem CellsPopulationPopulation HeterogeneityProcessProliferatingPropertyProtocols documentationRegenerative capacityResolutionRoleSignal PathwaySignal TransductionSkeletal MuscleSomatic CellSpecific qualifier valueStriated MusclesSystemTestingTissuesTretinoinWorkadult stem celldesignexperimental studyfetalfiber cellimaging approachimaging studyin vitro Modelin vivoin vivo evaluationinduced pluripotent stem cellinsightmuscle regenerationmyogenesisprogenitorregeneration potentialregenerativesatellite cellself-renewalsingle cell analysissingle cell sequencingsingle-cell RNA sequencingstem cellstranscriptomevirtual
项目摘要
SUMMARY/ABSTRACT
Adult skeletal muscle is endowed with significant regenerative capacity due to the presence of adult stem
cells, called satellite cells (SCs). Very little is known about the developmental origin of these cells in humans
and most of our knowledge derives from work performed in mouse. SCs are rare and they cannot be
amplified in unlimited numbers, as they lose their regenerative potential in vitro. These issues have
constituted a major roadblock for the study of their regenerative properties in humans and for the
development of translational applications, such as cell therapy.
The discovery that somatic cell reprogramming can be used to generate virtually endless numbers of cells
(iPSCs) has brought new hope for developing strategies allowing to study these processes in human cells.
We have recently developed efficient protocols to differentiate mouse and human embryonic pluripotent
stem cells (ES and iPS) into striated muscle fibers and SCs in vitro [1, 6]. The present proposal aims to take
advantage of these in vitro models combined with in vivo studies in mice to understand the development of
the SC lineage in humans.
In mouse, SCs constitute a heterogeneous population comprising a minor fraction of dormant cells with
important regenerative capacity and a faster dividing larger population. Whether this heterogeneity is
conserved in human is not known. Moreover, the developmental origin of this heterogeneity is not
understood. Thus an important aim of the proposed project is to understand the developmental basis of this
heterogeneity. We will compare the heterogeneity of mouse Pax7+ myogenic precursors developing in vivo
and in vitro using a newly introduced method of single cell sequencing (InDrop) which allows to sequence
thousands of cells in one experiment. A parallel analysis will be performed comparing human SCs
differentiated in vitro to fetal and adult human muscle tissue. These studies are expected to reveal the
developmental trajectories and the heterogeneity of the Pax7+ subpopulations in mouse and human SCs.
We will also take advantage of our in vitro myogenic differentiation systems to perform high-resolution live-
imaging studies of the development of the PAX7+ lineage. We will characterize poorly documented aspects
of SC differentiation such as their entry in quiescence and their contribution to myotubes. Finally, we have
identified Retinoic Acid (RA) and its co-activator complex WHHERE as a pathway able to induce reversible
quiescence in PAX7+ cells differentiated in vitro. The role of RA in the differentiation and the maintenance of
the PAX7+ lineage has not been investigated and we propose to characterize its function in vitro and in vivo
in developing and mature SCs. We expect our work to shed light on the development and function of the
human SC lineage, which could have significant implications for the development of cell-based therapies for
muscle diseases.
摘要/文摘
项目成果
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OLIVIER POURQUIE其他文献
OLIVIER POURQUIE的其他文献
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{{ truncateString('OLIVIER POURQUIE', 18)}}的其他基金
Regulators of Development and Quiescence in the Human Muscle Stem Cell Lineage
人类肌肉干细胞谱系发育和静止的调节因子
- 批准号:
10478923 - 财政年份:2019
- 资助金额:
$ 60.95万 - 项目类别:
Regulators of Development and Quiescence in the Human Muscle Stem Cell Lineage
人类肌肉干细胞谱系发育和静止的调节因子
- 批准号:
10684711 - 财政年份:2019
- 资助金额:
$ 60.95万 - 项目类别:
Regulators of Development and Quiescence in the Human Muscle Stem Cell Lineage
人类肌肉干细胞谱系发育和静止的调节因子
- 批准号:
10025167 - 财政年份:2019
- 资助金额:
$ 60.95万 - 项目类别:
Role of Energy Metabolism in Patterning the Vertebrate Musculo-Skeletal Axis
能量代谢在脊椎动物肌肉骨骼轴模式中的作用
- 批准号:
10211585 - 财政年份:2016
- 资助金额:
$ 60.95万 - 项目类别:
Role of Energy Metabolism in Patterning the Vertebrate Musculo-Skeletal Axis
能量代谢在脊椎动物肌肉骨骼轴模式中的作用
- 批准号:
10391546 - 财政年份:2016
- 资助金额:
$ 60.95万 - 项目类别:
Role of Energy Metabolism in Patterning the Vertebrate Musculo-Skeletal Axis
能量代谢在脊椎动物肌肉骨骼轴模式中的作用
- 批准号:
10611379 - 财政年份:2016
- 资助金额:
$ 60.95万 - 项目类别:
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