细胞死亡基因对人类疾病现象的广泛影响
Abigail L Rich1,2, Phillip Lin3,4, Eric R Gamazon5,6
1Department of Pathology, Microbiology & Immunology, Vanderbilt University Medical Center, Nashville, TN, USA.
Cell death & disease
|April 8, 2024
概括
基因调节的细胞死亡途径显示出独特的组织表达,并与数百种人类特征联系在一起,特别是血液细胞参数. 这揭示了细胞死亡基因.
科学领域:
- 遗传学和分子生物学
- 人体生理学 人体生理学
- 系统生物学 系统生物学
背景情况:
- 细胞死亡途径 (亡,亡,烧亡) 对于组织健康至关重要,但它们的组织特异性和疾病联系仍然不清楚.
- 了解人类组织中细胞死亡的遗传调节对于破译其在健康和疾病中的作用至关重要.
研究的目的:
- 在49个人类组织中绘制细胞死亡基因的表达景观.
- 研究基因调控细胞死亡基因表达与人类表型之间的关联,包括临床诊断和血液学参数.
主要方法:
- 使用GTEx数据对49个人类组织的细胞死亡基因表达特征进行分析.
- 来自英国生物库的500,000名个体的全转录组关联研究 (TWAS) 将基因表达与513个人类特征联系起来.
- 在BioVU生物库 (n=94,474) 中发现的独立验证.
主要成果:
- 在不同的人类组织类型中确定了独特的细胞死亡基因表达模式.
- 在基因调节细胞死亡基因表达和人类表型 (FDR <0.05) 之间发现了数百个显著的关联.
- 发现细胞死亡基因,特别是亡相关基因与血液特征 (白细胞和血小板参数) 的显著丰富.
结论:
- 细胞死亡基因表现出组织特异性表达,表明在组织生理学中具有不同的作用.
- 基因调节的细胞死亡基因表达与广泛的人类表型显著相关.
- 这些发现凸显了细胞死亡途径在人类健康和疾病,特别是血液学特征中的关键和多样化的作用.
相关概念视频
01:30Overview of Cell Death
7.3K
Cell death is an essential process where the body gets rid of old or damaged cells. Cell proliferation and death need to be balanced, as an imbalance between the two may lead to cancer or autoimmune diseases.
Cell death was observed in the early 19th century, but there was no experimental evidence to prove it. In 1842, Carl Vogt first discovered cell death in a metamorphic toad; however, it was not termed ‘cell death.’ Scientists discovered different cell death pathways only in the...
Cell death was observed in the early 19th century, but there was no experimental evidence to prove it. In 1842, Carl Vogt first discovered cell death in a metamorphic toad; however, it was not termed ‘cell death.’ Scientists discovered different cell death pathways only in the...
7.3K
02:26Protein Networks
3.9K
An organism can have thousands of different proteins, and these proteins must cooperate to ensure the health of an organism. Proteins bind to other proteins and form complexes to carry out their functions. Many proteins interact with multiple other proteins creating a complex network of protein interactions.
These interactions can be represented through maps depicting protein-protein interaction networks, represented as nodes and edges. Nodes are circles that are representative of a protein,...
These interactions can be represented through maps depicting protein-protein interaction networks, represented as nodes and edges. Nodes are circles that are representative of a protein,...
3.9K
01:30Apoptosis
11.4K
Apoptosis is a combination of two Greek words, 'apo' and 'ptosis,' meaning separation and falling off, respectively. Hippocrates used this word to describe gangrene, which was caused due to bandaging of fractured bones. Apoptosis was distinguished from necrosis in 1970 when John Kerr reported observations of morphological changes occurring during apoptosis. During one experiment, he observed that the disruption of blood supply to the liver tissue resulted in a size...
11.4K
01:24Caspases
12.5K
Caspase, a family of cysteine proteases, serve as effectors in apoptosis. The ced3 gene in C.elegans was first identified to be involved in apoptosis. This gene encodes the ced-3 caspase that is similar to the interleukin-1-beta converting enzyme or ICE in mammals. In addition to apoptosis, caspases also function in the inflammatory response. Inflammatory caspases are essential in activating pro-inflammatory cytokines that recruit immune cells and block the replication of pathogens inside...
12.5K
01:31The Intrinsic Apoptotic Pathway
6.5K
Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
6.5K
01:17The Extrinsic Apoptotic Pathway
6.3K
The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
6.3K