Towards Understanding Molecular Mechanisms of Human Hematopoietic Stem Cells' Quiescence
理解人类造血干细胞静止的分子机制
基本信息
- 批准号:10346063
- 负责人:
- 金额:$ 33.8万
- 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:2022-02-15 至 2025-01-31
- 项目状态:未结题
- 来源:
- 关键词:AgeAutophagocytosisBloodCell CycleCell Surface ReceptorsCell TherapyCellsClinicCommunicationDiseaseFoundationsGenerationsGenomicsGoalsHealthHematopoietic Stem Cell TransplantationHematopoietic Stem Cell subsetsHematopoietic stem cellsHomeostasisHumanImageInjuryInterventionLifeLinkLongevityLysosomesMaintenanceMalignant NeoplasmsMediatingMembrane PotentialsMetabolic stressMitochondriaMolecularMusOrganellesOutputPathway interactionsPhenotypePluripotent Stem CellsProcessPropertyRecyclingRegulationSurfaceTestingTimeTissuesTranslationsTransplantationWorkadult stem cellbasedesignhematopoietic stem cell fatehematopoietic stem cell quiescenceimprovedin vivomitochondrial membranenovelnovel strategiesprogramsrepairedreplication stressresponseself-renewalstem cell engraftmentstem cell functionstem cell therapystem cellsstem-like cellsuccesstherapy resistant
项目摘要
SUMMARY/ABSTRACT
Hematopoietic stem cells (HSCs) produce all blood lineages and replenish blood in response to loss or injury
throughout life. HSCs like most adult stem cells, are mainly quiescent. Quiescence is proposed to protect
HSCs from replicative and metabolic stress that would otherwise impact health and longevity, thereby
enabling them to maintain tissue homeostasis and allowing for the repair of defective/damaged tissue during
their lifetime. Progress in HSC-based therapies is partly hindered by lack of reliable approaches to modulate
HSC quiescence and activity. Thus, understanding the core molecular mechanisms of HSC quiescence is
fundamental for improving HSC health and longevity and has major translational implications for the clinic.
By applying a new approach based on mitochondrial membrane potential (MMP), we identified the most
dormant subsets of both human and mouse HSCs. Using this approach, we recently discovered that
lysosomal activity is pivotal for the maintenance of mouse HSC quiescence. Our findings suggest that
lysosomes dynamically regulate the hematopoietic stem cell switch between quiescent and active states.
Here, we propose to investigate lysosomal function and the effects of modulation of lysosomal activity on the
potency of human HSCs. These studies are likely to provide means towards extending the availability of
human HSCs. Overall, translation of our findings to human HSCs will build the foundation towards advancing
cell therapy.
摘要/摘要
造血干细胞 (HSC) 产生所有血统并补充血液以应对损失或受伤
一生。与大多数成体干细胞一样,HSC 主要处于静止状态。建议静止以保护
HSCs 免受复制和代谢压力的影响,否则会影响健康和寿命,从而
使它们能够维持组织稳态并允许修复有缺陷/受损的组织
他们的一生。基于 HSC 的疗法的进展部分由于缺乏可靠的调节方法而受到阻碍
HSC 静止和活动。因此,了解 HSC 静止的核心分子机制是
是改善 HSC 健康和寿命的基础,对临床具有重大转化意义。
通过应用基于线粒体膜电位 (MMP) 的新方法,我们确定了最
人类和小鼠 HSC 的休眠子集。使用这种方法,我们最近发现
溶酶体活性对于维持小鼠 HSC 静止至关重要。我们的研究结果表明
溶酶体动态调节造血干细胞在静止和活跃状态之间的转换。
在这里,我们建议研究溶酶体功能以及溶酶体活性调节对
人类 HSC 的效力。这些研究可能会提供扩大可用性的方法
人类造血干细胞。总体而言,将我们的研究结果转化为人类 HSC 将为进一步发展奠定基础
细胞疗法。
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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SAGHI GHAFFARI其他文献
SAGHI GHAFFARI的其他文献
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{{ truncateString('SAGHI GHAFFARI', 18)}}的其他基金
Towards Understanding Molecular Mechanisms of Human Hematopoietic Stem Cells' Quiescence
理解人类造血干细胞静止的分子机制
- 批准号:
10570203 - 财政年份:2022
- 资助金额:
$ 33.8万 - 项目类别:
FOXO3 Regulation of Normal and Stress Erythropoiesis
FOXO3 对正常和应激性红细胞生成的调节
- 批准号:
9264330 - 财政年份:2017
- 资助金额:
$ 33.8万 - 项目类别:
Mitochondria in the Regulation of Terminal Erythropoiesis
线粒体对终末红细胞生成的调节
- 批准号:
10587056 - 财政年份:2017
- 资助金额:
$ 33.8万 - 项目类别:
FOXO3 Regulation of Normal and Stress Erythropoiesis
FOXO3 对正常和应激性红细胞生成的调节
- 批准号:
9403199 - 财政年份:2017
- 资助金额:
$ 33.8万 - 项目类别:
(PQ5) Mitochondria in Leukemic Stem Cell Disease Progression
(PQ5) 白血病干细胞疾病进展中的线粒体
- 批准号:
9336279 - 财政年份:2016
- 资助金额:
$ 33.8万 - 项目类别:
(PQ5) Mitochondria in Leukemic Stem Cell Disease Progression
(PQ5) 白血病干细胞疾病进展中的线粒体
- 批准号:
9753161 - 财政年份:2016
- 资助金额:
$ 33.8万 - 项目类别:
Lysosomes and their Communications with Mitochondria in Leukemic Stem Cell Disease Progression
白血病干细胞疾病进展中的溶酶体及其与线粒体的通讯
- 批准号:
10688239 - 财政年份:2016
- 资助金额:
$ 33.8万 - 项目类别:
(PQ5) Mitochondria in Leukemic Stem Cell Disease Progression
(PQ5) 白血病干细胞疾病进展中的线粒体
- 批准号:
9172951 - 财政年份:2016
- 资助金额:
$ 33.8万 - 项目类别:
Lysosomes and their Communications with Mitochondria in Leukemic Stem Cell Disease Progression
白血病干细胞疾病进展中的溶酶体及其与线粒体的通讯
- 批准号:
10522534 - 财政年份:2016
- 资助金额:
$ 33.8万 - 项目类别:
AKT Signaling and Oxidative Stress Regulation of Erythropoiesis
AKT 信号传导和红细胞生成的氧化应激调节
- 批准号:
8470631 - 财政年份:2009
- 资助金额:
$ 33.8万 - 项目类别: