对体质突变克隆的积极选择确定了代谢性肝病的适应途径
Zixi Wang1, Shijia Zhu2, Yuemeng Jia1
1Children's Research Institute, Departments of Pediatrics and Internal Medicine, Center for Regenerative Science and Medicine, Simmons Comprehensive Cancer Center, Children's Research Institute Mouse Genome Engineering Core, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Cell
|April 11, 2023
概括
身体突变可能是适应性的. 研究人员开发了一种小鼠模型来识别保护非酒精性脂肪肝炎 (NASH) 诱导的脂毒性基因,揭示了代谢疾病的关键途径.
科学领域:
- 遗传学
- 代谢疾病研究
- 细胞生物学
背景情况:
- 随着年龄和损伤,体内突变会累积,但它们的适应性作用仍然不清楚.
- 研究这些突变对于了解非酒精性脂肪肝炎 (NASH) 等人类代谢疾病至关重要.
研究的目的:
- 在人体代谢疾病中涉及的基因使用体质马赛克的小鼠模型进行调查.
- 在NASH的背景下识别细胞或生物适应的基因突变.
主要方法:
- 在接受NASH的体质马赛克的小鼠中开发了一个谱系追踪平台 (MOSAICS).
- 在63个已知的NASH基因中进行了聚合马赛克,并选了472个候选者.
- 通过整个肝脏的删除研究验证了保护基因.
主要成果:
- 在NASH模型中,Mboat7的马赛克损失加速了克隆的消失.
- MOSAICS平台选择了改善脂毒性的突变,包括已知的人类NASH基因.
- 鉴定了23种促进克隆扩张的体质干扰,其中Tbx3,Bcl6和Smyd2的缺失可以防止肝硬化.
结论:
- 在小鼠和人类肝脏中的细胞适应性选择确定了调节代谢疾病的新途径.
- MOSAICS平台是一个强大的工具,用于在疾病背景下发现适应性体质突变.
- 针对涉及Tbx3,Bcl6和Smyd2的已知途径可能为NASH提供治疗策略.
相关概念视频
Adaptive Mechanisms in Cancer Cells
5.9K
Cancer cells accumulate genetic changes at an abnormally rapid rate due to the defects in the DNA repair mechanisms. From an evolutionary perspective, such genetic instability is advantageous for cancer development. Mutant cell lines accumulate a series of beneficial mutations that contribute to their progression into cancer.
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
5.9K
mTOR Signaling and Cancer Progression
3.8K
The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
The mTOR pathway or the...
3.8K
Targeted Cancer Therapies
7.7K
The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
There are several types of targeted therapies against...
7.7K
Liver Regeneration
3.3K
The liver is an important organ in vertebrates that plays an essential role in metabolism. It is also responsible for storing and redistributing nutrients such as carbohydrates, fats, and vitamins in the body. Additionally, the liver releases bile salts which are critical for digesting food and eliminating toxic metabolites from the body.
Cells of Liver
The liver comprises four major types of cells— hepatocytes, stellate, Kupffer, and sinusoidal endothelial cells. The hepatocytes are...
Cells of Liver
The liver comprises four major types of cells— hepatocytes, stellate, Kupffer, and sinusoidal endothelial cells. The hepatocytes are...
3.3K
Cancers Originate from Somatic Mutations in a Single Cell
12.3K
Cancer arises from mutations in the critical genes that allow healthy cells to escape cell cycle regulation and acquire the ability to proliferate indefinitely. Though originating from a single mutation event in one of the originator cells, cancer progresses when the mutant cell lines continue to gain more and more mutations, and finally, become malignant. For example, chronic myelogenous leukemia (CML) develops initially as a non-lethal increase in white blood cells, which progressively...
12.3K
Combination Therapies and Personalized Medicine
5.0K
Combining two or more treatment methods increases the life span of cancer patients while reducing damage to vital organs or tissue from the overuse of a single treatment. Combination therapy also targets different cancer-inducing pathways, thus reducing the chances of developing resistance to treatment.
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
5.0K


