人体体细胞的重编程,以具有定义因素的多能性
In-Hyun Park1, Rui Zhao, Jason A West
1Division of Pediatric Hematology/Oncology, Children's Hospital Boston and Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA.
Nature
|December 25, 2007
概括
科学家们使用四个特定因素将人类细胞重新编程成诱导多能干细胞 (iPS). 这一突破使得研究和潜在治疗的患者特异性细胞生成成为可能.
科学领域:
- 细胞生物学 细胞生物学
- 发展生物学 发展生物学
- 干细胞研究 干细胞研究
背景情况:
- 多能性是细胞分化成任何细胞类型的能力.
- 胚胎干细胞对于理解组织形成至关重要.
- 诱导多能干细胞 (iPS) 提供了一个新的研究途径.
研究的目的:
- 从人类的原始细胞中提取iPS细胞.
- 研究人类细胞中定义的转录因子的重编程潜力.
- 建立一种产生患者特异性的多能细胞的方法.
主要方法:
- 在子宫外表达Oct4,Sox2,Klf4和Myc转录因子.
- 重编程胎儿,新生儿和成年人的皮肤纤维细胞.
- 通过形态学,基因表达和瘤形成对衍生人类iPS细胞的表征.
主要成果:
- 从各种原始人类细胞类型中成功生成了人类iPS细胞.
- 人类iPS细胞表现出与胚胎干细胞相似的特征.
- 在体内证明了瘤形成的能力.
结论:
- 定义的转录因子可以将人体体细胞重新编程到多能状态.
- 这种方法为创建患者特定的iPS细胞提供了一条途径.
- 它为再生医学和疾病建模提供了巨大的潜力.
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相关概念视频
01:29Somatic to iPS Cell Reprogramming
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 for this...
01:24Methods of Nuclear Reprogramming
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 injury repair.
01:32Chromatin Modification in iPS Cells
Chromatin modification alters gene expression; therefore, scientists can add histone-modifying enzymes, histone variants, and chromatin remodeling complexes to somatic cells to aid reprogramming into pluripotent stem (iPS) cells.
Compact chromatin makes reprogramming difficult. Enzymes, such as histone demethylases and acetyltransferases, are often added during reprogramming to loosen the chromatin, making the DNA more accessible to transcription factors. Molecules that inhibit histone...
Compact chromatin makes reprogramming difficult. Enzymes, such as histone demethylases and acetyltransferases, are often added during reprogramming to loosen the chromatin, making the DNA more accessible to transcription factors. Molecules that inhibit histone...
01:06Induced Pluripotent Stem Cells
Stem cells are undifferentiated cells that divide and produce different cell types. Ordinarily, cells that have differentiated into a specific cell type are terminally differentiated; however, scientists have found a way to reprogram these mature cells so that they dedifferentiate and return to an unspecialized, proliferative state. These cells are pluripotent like embryonic stem cells—able to produce all cell types—and are called induced pluripotent stem cells (iPSCs).
Somatic cells are...
Somatic cells are...
01:13Induced Pluripotent Stem Cells
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 called induced pluripotent stem...
01:13Induced Pluripotent Stem Cells
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 called induced pluripotent stem...