重编程以恢复年轻的表观遗传信息并恢复视力
Yuancheng Lu1, Benedikt Brommer2,3, Xiao Tian1
1Department of Genetics, Blavatnik Institute, Paul F. Glenn Center for Biology of Aging Research, Harvard Medical School, Boston, MA, USA.
Nature
|December 3, 2020
概括
科学家使用特定的基因重编程恢复了老鼠眼睛的青春表观遗传模式. 这改善了视力和神经再生,
科学领域:
- 表观遗传学和衰老研究
- 神经科学和再生医学
- 分子生物学和基因表达
背景情况:
- 衰老导致组织功能障碍和再生能力丧失,部分原因是表观遗传噪声的积累.
- DNA甲基化模式随着年龄的增长而变化,
- 目前尚不清楚老年组织是否保留信息以恢复年轻的表观遗传模式并改善功能.
研究的目的:
- 研究老鼠视网膜细胞中的特定基因是否可以恢复年轻的表观遗传模式和功能.
- 确定这种重新编程能否增强组织再生并逆转与年龄相关的视力损失.
- 探索DNA脱甲基酶TET1和TET2在OSK诱导的重编程效益中的作用.
主要方法:
- 在小鼠视网膜细胞中,Oct4 (Pou5f1),Sox2和Klf4基因 (OSK) 的异位表达.
- 对DNA甲基化模式和转录组进行分析以评估表观遗传修复.
- 在青光眼和老鼠模型中评估受伤后的轴突再生和视力恢复.
- 调查 TET1 和 TET2 DNA 脱甲基酶对于观察到的功能改善的必要性.
主要成果:
- 在老年视网膜细胞中,OSK基因表达恢复了年轻的DNA甲基化模式和转录组.
- 在青光眼和老年小鼠中,重编程促进了伤害后的轴突再生和逆转视力丧失.
- OSK的促再生和视力恢复作用取决于DNA脱甲基酶TET1和TET2.
结论:
- 哺乳动物组织保留了年轻的表观遗传信息,部分由DNA甲基化编码.
- 这种表观遗传信息可以通过基因重编程来改善组织功能并促进体内再生.
- 针对表观遗传机制提供了与年龄相关的衰退和增强再生能力的潜在策略.
更多相关视频
相关概念视频
01:29Somatic to iPS Cell Reprogramming
2.4K
Reprogramming alters the gene expression in somatic cells, transforming them into induced pluripotent stem (iPS) cells over several generations. Scientists can reprogram cells by introducing genes for four transcription factors—Oct4, Sox2, Klf4, and c-Myc (OSKM) by viral or non-viral methods. These factors are also known as Yamanaka factors after Shinya Yamanaka, who first generated iPS cells using mouse skin cells. Yamanaka was awarded the Nobel Prize in Physiology or Medicine in 2012...
2.4K
01:24Methods of Nuclear Reprogramming
2.0K
Nuclear reprogramming is a process of transforming one cell type into an unrelated cell type by epigenetic changes that alter the cell’s original gene expression pattern. Such epigenetic changes force cells to express a different set of genes, which play a significant role in inducing transformation into other cell types. Nuclear reprogramming offers applications in reproductive cloning for livestock propagation and regenerative medicine — developing patient-specific cells for...
2.0K
01:14Introduction to Nuclear Reprogramming
2.1K
Nuclear reprogramming is the process of switching gene expression of one cell type to that of another cell type, usually from a differentiated cell state to an undifferentiated cell state. Differentiation occurs during processes such as development and morphogenesis, tissue regeneration, and malignancy. Cells can also be artificially induced to reprogram their gene expression by techniques such as nuclear transfer, induced pluripotency, and cell fusion. Such techniques have many applications in...
2.1K
01:12Renewal of Skin Epidermal Stem Cells
2.8K
The skin is divided into epidermis, dermis, and hypodermis, the skin's outermost, middle, and inner layers. The human epidermal layer regularly undergoes renewal, where old, dead cells are replaced by new cells. Epidermal stem cells or EpiSCs divide and differentiate to restore the lost cells. For the renewal process, some EpiSCs continuously self-renew. In contrast, few others differentiate into transit-amplifying cells, which later form prickle or spinous cells, followed by granular...
2.8K
01:33Whole Body Regeneration
3.8K
Regeneration is the process of restoring injured or lost tissues, organs, or body parts. While simpler organisms generally show greater ability to regenerate their whole body, few complex animals show similarly exceptional regeneration. For example, planarian flatworms have a unique regenerative potential making them a popular study organism among biologists to understand the mechanisms of whole body regeneration. Other organisms, such as hydra, also show extreme regeneration potential;...
3.8K
01:22iPS Cell Differentiation
2.9K
The ability of induced pluripotent stem cells or iPSCs to differentiate into most body cell types has stimulated repair and regenerative medicine research over the past few decades. iPSC-derived blood cells, hepatocytes, beta islet cells, cardiomyocytes, neurons, and other cell types can repair injuries or regenerate damaged tissue in diseases such as diabetes and neurodegenerative disorders.
2.9K