FOXO3A指导血液形成干细胞中的保护性自程序
Matthew R Warr1, Mikhail Binnewies, Johanna Flach
1The Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, Department of Medicine, Division of Hematology/Oncology, University of California San Francisco, San Francisco, California 94143, USA.
Nature
|February 8, 2013
概括
自能保护罕见的造血干细胞 (HSC) 免受压力. 这一由FOXO3A调节的必不可少的过程,确保了HSC的生存和血液系统的功能,在整个生命中,即使在衰老.
科学领域:
- 血液学 血液学 血液学
- 细胞生物学 细胞生物学
- 衰老研究研究 衰老研究
背景情况:
- 造血干细胞 (HSC) 对于终身血液生产至关重要.
- 人们还没有完全理解高细胞应对细胞压力的机制.
研究的目的:
- 调查自在保护高细胞免受代谢压力的作用.
- 确定HSC中自的关键调节者.
主要方法:
- 在小鼠HSC中诱导自的比较分析与髓状后代.
- 在细胞因子撤销和卡路里限制条件下,评估HSC的自.
- 调查FOXO3A在调节HSC中自相关基因表达中的作用.
主要成果:
- 高细胞在应对代谢压力时强烈诱导自,与它们的后代不同.
- 在HSC中,FOXO3A对于维持自基因表达程序至关重要.
- 衰老的高细胞依靠正在进行的自来管理能量赤字并确保生存.
结论:
- 自是HSCs对代谢压力的关键保护机制.
- 由FOXO3A驱动的亲自食途径对于HSC的维护和功能至关重要.
- 自对于支持衰老的血液系统和缓解与年龄相关的HSC衰退是不可或缺的.
相关概念视频
Autophagy
Autophagy is a self-digesting process by which a cell protects itself from threats both within and outside the cell, ranging from abnormal proteins to invading bacteria. In this process, obsolete components of the cell and invading microbes are degraded by hydrolytic enzymes active in an acidic environment of the lysosomal lumen.
An autophagic pathway consists of a series of signaling events activated in response to diverse stress and physiological conditions such as food deprivation,...
An autophagic pathway consists of a series of signaling events activated in response to diverse stress and physiological conditions such as food deprivation,...
Autophagic Cell Death
Christian de Duve discovered “autophagy,” a process in which cellular components are engulfed by membrane-bound organelles called autophagosomes. The autophagosomes then fuse with lysosomes to digest the enclosed contents. Autophagy is generally activated in cells to prevent cell death. However, cell death is triggered when the damage is beyond repair.
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and pro-apoptotic...
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and pro-apoptotic...
Regulation of Hematopoietic Stem Cells
All blood and immune cells are produced from the multipotent hematopoietic stem cells (HSCs) by the process of hematopoiesis. However, they all have a limited life span. In addition, many are depleted in immune surveillance or combatting an injury or infection. This makes blood one of the most regenerative tissues. Hematopoiesis helps replenish these blood and immune cells, restoring the body's normal functioning. However, overproduction of blood and immune cells can make them cancerous or...
Delivery Pathways to the Lysosome
Eukaryotic cells use different mechanisms to eliminate toxic waste obsolete and worn-out substances. Lysosomes play a pivotal role in this, and hence, these substances are carried to the lysosome from other parts of the cell and extracellular space through different pathways. The most elaborately studied pathways to the lysosome are the endocytic pathways.
Endocytosis
In endocytosis, the cell membrane takes up macromolecules and particles from the surrounding medium. Clathrin-mediated...
Endocytosis
In endocytosis, the cell membrane takes up macromolecules and particles from the surrounding medium. Clathrin-mediated...
Regulation of Angiogenesis and Blood Supply
Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits. Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl hydroxylase and factor...
Cellular Injury V: Apoptosis and Autophagy
Cells respond to damage and stress through highly coordinated processes that decide whether they survive or undergo controlled self-destruction. Two major pathways involved in this regulation are apoptosis, a type of programmed cell death, and autophagy, a survival mechanism that helps cells adapt to adverse conditions.ApoptosisApoptosis removes aged or injured cells to maintain tissue balance. During this process, the cell shrinks, chromatin condenses and fragments, and membrane-bound...


