表观遗传和蛋白质特征与克隆性血液形成扩张率相关
Taralynn M Mack1, Michael A Raddatz1,2, Yash Pershad1
1Vanderbilt Genetics Institute, Vanderbilt University School of Medicine, Nashville, TN, USA.
Nature aging
|June 4, 2024
概括
不确定潜力 (CHIP) 扩张的克隆性血液形成与遗传因素有关. 这项研究确定了影响CHIP克隆生长率的表观遗传钟和特定蛋白质,为造血干细胞动态提供了新的见解.
科学领域:
- 血液学 血液学 血液学
- 遗传学 是一个遗传学.
- 衰老研究研究 衰老研究
背景情况:
- 不确定潜力的克隆造血 (CHIP) 涉及血液造血干细胞的体质突变,导致克隆扩张.
- CHIP与衰老和增加发病率和死亡率风险有关.
研究的目的:
- 通过使用遗传预测的特征来确定影响CHIP克隆扩张率的因素.
- 调查表观遗传衰老,炎症和蛋白质水平与CHIP扩张之间的关系.
主要方法:
- 从NHLBI TOPMed队列中的4,370个人中使用乘客近似的克隆扩张率方法量化CHIP的克隆扩张率.
- 计算了DNA甲基化衰老,炎症和循环蛋白质的多基因风险得分.
- 进行了全蛋白质组的关联研究,以确定与CHIP扩张率的蛋白质关联.
主要成果:
- CHIP的克隆扩张率与基因预测和测量的表观遗传钟有显著的关联.
- 在与炎症相关的因素和CHIP扩张率之间没有发现整体关联.
- 特定的蛋白质,包括骨髓性指1和抗穆勒尔激素,与CHIP扩张的增加有关,而金属蛋白酶1和甘氨酸N-甲基转移酶的组织抑制剂与扩张的减少有关.
结论:
- 表观遗传模式,特别是表观遗传时钟,与造血细胞克隆扩张的速度有关.
- 特定的循环蛋白水平与CHIP克隆扩张率的增加和减少有关.
- 这些发现突出了基因,表观遗传学和蛋白质学在调节CHIP进展中的相互作用.
相关概念视频
01:21Hematopoiesis
5.2K
The process of blood cell formation is called hematopoiesis. Hematopoiesis starts early during development, on the seventh day of embryogenesis. This phase of hematopoiesis is called the primitive wave, wherein the extraembryonic yolk sac allows the production of erythroid cells and endothelial cells from a common precursor called hemangioblast. The erythroid cells provide oxygen to support the growth of the rapidly dividing embryo. Hemangioblasts later develop into hematopoietic stem cells or...
5.2K
01:28Role of Hematopoietic Growth Factors
1.4K
Hematopoietic growth factors are molecules that regulate the differentiation rate of hematopoietic stem cells (HSCs). Erythropoietin (EPO), primarily produced by the kidneys, plays a crucial role in erythrocyte production. When oxygen levels in the blood are low, EPO is released into the bloodstream, reaching the bone marrow, where it stimulates HSCs to differentiate and mature into erythrocytes, which are vital for oxygen transport.
Thrombopoietin (TPO), mainly released by the liver,...
Thrombopoietin (TPO), mainly released by the liver,...
1.4K
01:21Lineage Commitment
3.0K
Commitment is the process whereby stem cells:
3.0K
01:01Regulation of Hematopoietic Stem Cells
3.2K
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...
3.2K
01:19Multipotency of Hematopoietic Stem Cells
3.1K
The hematopoietic stem cells or HSCs are multipotent, meaning they can differentiate and give rise to all blood and immune cells. HSCs are maintained in the quiescent stage until an external stimulus initiates their differentiation. The multipotent HSCs exist as two heterogeneous populations, long-term repopulating cells (LTRC) and short-term repopulating cells (STRC). The two HSC populations have different surface markers or receptors and are classified based on quiescence and long-term...
3.1K