身体的に変異したクローンの正の選択は,代謝性肝疾患における適応経路を特定する
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
まとめ
体内の変異は適応性がある 研究者は,非アルコール性脂肪肝炎 (NASH) 誘発性脂質毒性に対する保護遺伝子を識別するためにマウスモデルを開発し,代謝疾患の重要な経路を明らかにしました.
科学分野:
- 遺伝学
- 代謝疾患の研究
- 細胞生物学
背景:
- 体内の突然変異は年齢や傷つきと共に蓄積しますが その適応的役割は不明です
- これらの変異の調査は,非アルコール性脂肪肝炎 (NASH) などのヒトの代謝疾患を理解するために不可欠です.
研究 の 目的:
- ヒトの代謝疾患に関与する遺伝子を,ソマティック・モザイクのマウスモデルを用いて調査する.
- NASHの文脈で細胞または生物の適応を与える遺伝的変異を特定する.
主な方法:
- NASH に罹患したソマティック・モザイク症のマウスにおいて,系統追跡プラットフォーム (MOSAICS) を開発した.
- 63の既知のNASH遺伝子でモザイク分析を行い,472の候補者をスクリーニングした.
- 肝臓全体で保護遺伝子を検証した
主要な成果:
- モザイクによるMboat7の喪失は,NASHモデルにおけるクローンの消失を加速した.
- MOSAICSプラットフォームは,既知のヒトNASH遺伝子を含め,脂質毒性を改善する変異を選択しました.
- Tbx3,Bcl6およびSmyd2の欠失が肝臓ステアトーシスから保護する23の身体的障害を特定した.
結論:
- マウスとヒトの肝臓における細胞フィットネス選択は,代謝疾患を調節する新しい経路を特定します.
- MOSAICSプラットフォームは,病気の状況における適応性ソマティック変異の発見のための強力なツールです.
- Tbx3,Bcl6,Smyd2を含むような特定された経路をターゲットにすることで,NASHの治療戦略を提供することができます.
関連する概念動画
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


