克隆性血液形成的人类血蛋白质谱
Zhi Yu1,2, Amélie Vromman3, Ngoc Quynh H Nguyen4,5
1Broad Institute of MIT and Harvard, Cambridge, MA, USA.
bioRxiv : the preprint server for biology
|November 18, 2024
概括
血液细胞的亚临床突变,称为克隆性血液形成 (CHIP),与冠状动脉疾病有关. 这项研究确定了与CHIP相关的血蛋白,揭示了免疫和炎症途径的参与以及与冠状动脉疾病共享的蛋白质.
科学领域:
- 遗传学 遗传学 是一个
- 蛋白质组学是指蛋白质组学.
- 心血管疾病 心血管疾病
背景情况:
- 不确定潜力的克隆性血液形成 (CHIP) 涉及血液细胞的亚临床体质突变.
- CHIP与不良健康结果有关,包括冠状动脉疾病 (CAD).
- 了解CHIP及其后果之间的分子联系对于临床见解至关重要.
研究的目的:
- 调查与CHIP相关的血蛋白质组概况.
- 确定与普遍存在的CHIP驱动基因 (DNMT3A,TET2,ASXL1) 相关的特定蛋白质.
- 探索CHIP和CAD之间共享的蛋白质组签名.
主要方法:
- 在NHLBI TOPMed和英国生物银行中分析了来自61,833名参与者的血蛋白质组数据 (3,881名参与者使用CHIP).
- 基于血液的DNA测序和蛋白质组测量 (SomaScan和Olink测试).
- 门德尔随机化和小鼠模型验证 (Tet2-/-与野生类型) 以确定因果关系.
主要成果:
- 确定了32种 (TOPMed) 和345种 (英国生物库) 独特的蛋白质,与CHIP驱动基因相关.
- 蛋白质关联表现出基于驱动基因,性别和种族的异质性.
- 丰富分析揭示了与免疫反应和炎症相关的途径.
- 确定了与TET2 CHIP相关的因果蛋白质干扰.
- 发现了CHIP和CAD队列中共同的血蛋白.
结论:
- 血蛋白质组形状与CHIP及其驱动突变有关.
- 免疫和炎症途径与CHIP病变发生有关.
- 特定的血蛋白质可以作为CHIP和相关疾病 (如CAD) 的生物标志物或治疗点.
相关概念视频
Hematopoiesis
5.1K
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...
5.1K
Overview of Hematopoiesis
3.8K
Hematopoiesis, or blood cell production, is a vital biological process that begins early in embryonic development and continues throughout life. This process generates the various types of cells found in blood, including red blood cells, white blood cells, and platelets from hematopoietic stem cells (HSCs).
Developmental Phases of Hematopoiesis
Initially, HSCs are formed in the embryonic yolk sac, a critical site for early blood cell production. These stem cells subsequently migrate to other...
Developmental Phases of Hematopoiesis
Initially, HSCs are formed in the embryonic yolk sac, a critical site for early blood cell production. These stem cells subsequently migrate to other...
3.8K
Production of Formed Elements
1.3K
Hemangioblasts are multipotent stem cells originating from the mesoderm. They give rise to hematopoietic stem cells (HSCs), which undergo hematopoiesis to produce all the formed elements of blood. This process is regulated by a complex network of hematopoietic growth factors, including transcription factors, growth factors, and cytokines. These factors stimulate the HSCs to divide and differentiate, though some HSCs remain undifferentiated to maintain a self-renewing pool.
Most HSCs commit to...
Most HSCs commit to...
1.3K
Multipotency of Hematopoietic Stem Cells
3.0K
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...
3.0K
Lineage Commitment
3.0K
Commitment is the process whereby stem cells:
3.0K


