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

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/文摘

项目成果

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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:
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:
    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:
(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:
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