piggyBac转换重新编程纤维细胞,诱导多能干细胞
Knut Woltjen1, Iacovos P Michael, Paria Mohseni
1Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario M5G 1X5, Canada.
Nature
|March 3, 2009
概括
通过使用piggyBac (PB) 转换系统,可以有效地将体细胞重新编程成诱导多能干细胞 (iPS). 这种病毒独立的方法可以无地去除重编程因子,推进基于细胞的疗法.
科学领域:
- 细胞生物学 细胞生物学
- 遗传学 是一个遗传学.
- 生物技术是生物技术.
背景情况:
- 四个转录因子 (c-Myc,Klf4,Oct4,Sox2) 诱导体细胞中的多能性.
- 目前的方法,如病毒或等离子体传染,在效率和安全方面存在局限性.
- PiggyBac (PB) 转换系统提供了一种独立于宿主因子的基因传递方法.
研究的目的:
- 通过PB转换系统,证明纤维细胞在诱导多能干细胞 (iPS) 中的高效重编程.
- 评估从已建立的iPS细胞系中去除PB插入的能力.
- 开发一种简化,病毒独立的iPS细胞生产方法.
主要方法:
- 通过PB转移到小鼠和人类胚胎纤维细胞中传递可诱导多克西环林的转录因子.
- 稳定的iPS细胞系的生成和表征.
- 评估多能性标记物和差异化潜力.
- 证明PB插入和重编程因子的无切除.
主要成果:
- 通过PB转移成功和有效地将纤维细胞重新编程成iPS细胞.
- 生成的iPS细胞表达了多能性标记物,并成功分化.
- 从iPS线路中证明了无痕去除PB插入和重编程因子.
- 实现了iPS细胞生产的病毒独立简化.
结论:
- PB转换为iPS细胞生成提供了一个高效和多功能平台.
- 能够去除PB元素对于治疗应用至关重要.
- 这种简化的,与病毒无关的方法加速了重编程和基于细胞的疗法领域的发展.
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...
01:13Induced 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...
01:06Induced 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...
01:24Methods 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.
01:28Forced Transdifferentiation
Transdifferentiation, also known as lineage reprogramming, was first discovered by Selman and Kafatos in 1974 in silkmoths. They observed that the moths’ cuticle-producing cells transformed into salt-producing cells. Many such cases of natural transdifferentiation occur in organisms. In humans, pancreatic alpha cells can become beta cells. In newts, the loss of the eye’s lens causes the pigmented epithelial cells to transdifferentiate into the lens cells.
Artificial transdifferentiation occurs...
Artificial transdifferentiation occurs...