拉A/C调节的氨酸催化流调节干细胞命运通过表观基因组重编程
Yinuo Wang1,2, Haojie Shi3, Janina Wittig4,5
1Department of Cardiovascular Genomics and Epigenomics, European Center for Angioscience (ECAS), Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany. Yinuo.Wang@medma.uni-heidelberg.de.
Nature metabolism
|January 28, 2026
概括
拉胺A/C调节囊的新陈代谢,影响细胞命运和寿命. 操纵囊酶 (CTH和CBS) 可以纠正异常的细胞功能和由细膜A/C突变引起的衰老表型.
科学领域:
- 细胞生物学 细胞生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 代谢调节 代谢调节 代谢调节
背景情况:
- 核膜和细胞代谢极大地影响细胞命运和寿命.
- 核膜蛋白和代谢途径之间的精确相互作用在很大程度上仍未被探索.
研究的目的:
- 为了研究层A/C在调节细胞代谢中的作用及其对细胞命运的影响.
- 为了阐明层A/C,氨酸代谢和表观遗传修饰之间的联系.
主要方法:
- 分析了层状A/C表达及其对多能干细胞的影响.
- 测量氨酸催化流和关键酶活性 (CTH,CBS).
- 评估组织组织蛋白修饰 (H3K9,H3K27乙化/甲基化) 和细胞命运标记.
主要成果:
- 拉胺A/C损失上调了囊氨酸合成酶 (CTH,CBS),增加了囊氨酸的流量和基因素乙化,推动了对原始多能性过渡的天真.
- 与过早衰老相关的lmna突变降低了CTH和CBS,改变了囊蛋白流量,H3K9平衡,并影响了胚胎层的形成和基因组的稳定性.
- 调节CTH和CBS水平可以拯救异常细胞表型,恢复DNA修复,并减轻层状A/C突变模型中的衰老.
结论:
- 拉敏A/C是氨酸代谢流的关键调节者,对维持细胞命运和寿命至关重要.
- 针对细胞代谢,特别是氨酸通路,为与核膜功能障碍相关的表观遗传疾病提供了治疗策略.
相关概念视频
01:01Regulation of Hematopoietic Stem Cells
4.1K
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...
4.1K
01:13Induced Pluripotent Stem Cells
28.0K
Stem cells are undifferentiated cells that divide and produce different types of cells. Ordinarily, cells that have differentiated into a specific cell type are post-mitotic—that is, they no longer divide. However, scientists have found a way to reprogram these mature cells so that they “de-differentiate” and return to an unspecialized, proliferative state. These cells are also pluripotent like embryonic stem cells—able to produce all cell types—and are therefore...
28.0K
01:30Carbohydrate Catabolism
1.1K
Carbohydrate catabolism is a fundamental process in cellular metabolism that enables energy extraction from glucose through two primary pathways: cellular respiration and fermentation. Both pathways begin with glycolysis, which operates independently of oxygen availability.Glycolysis: A Shared Starting PointGlycolysis is an oxygen-independent process that breaks down glucose into two molecules of pyruvic acid. During this process, a net gain of two ATP molecules and two NADH molecules is...
1.1K
01:25Lipid Catabolism
959
Triglycerides serve as crucial long-term energy storage molecules in microorganisms, providing a dense source of metabolic energy. Their breakdown is mediated by lipases, which hydrolyze triglycerides into glycerol and free fatty acids. Each of these components follows distinct metabolic pathways, ultimately contributing to ATP synthesis and cellular energy homeostasis.Glycerol MetabolismGlycerol, released from triglyceride hydrolysis, is phosphorylated by glycerol kinase to form...
959
02:04Covalently Linked Protein Regulators
9.5K
Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein....
These groups modify specific amino acids in a protein....
9.5K
01:18Amino Acid Catabolism
1.1K
Microorganisms rely on proteins as an essential carbon and energy source, particularly in environments with limited polysaccharides or lipids. However, proteins are too large to cross the plasma membrane unaided, necessitating enzymatic degradation. Microbes secrete extracellular proteases and peptidases that hydrolyze proteins into peptides, which can then be transported across the membrane. Once inside the cell, intracellular proteases degrade these peptides into free amino acids, which...
1.1K