一个全基因组RNAi屏幕揭示了人类胚胎干细胞身份的决定因素
Na-Yu Chia1, Yun-Shen Chan, Bo Feng
1Gene Regulation Laboratory, Genome Institute of Singapore, 60 Biopolis Street, Singapore 138672.
Nature
|October 19, 2010
概括
研究人员确定了调节人类胚胎干细胞 (hESC) 自新和多能性的关键基因. 发现PRDM14对于维持hESC身份和增强体细胞重编程至关重要.
科学领域:
- 干细胞生物学 干细胞生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 转录法规 转录法规
背景情况:
- 人类胚胎干细胞 (hESCs) 具有重要的研究和临床潜力.
- 了解控制hESC自我更新和多能性的遗传网络对于它们的应用至关重要.
研究的目的:
- 通过全基因组RNA干扰屏幕识别调节hESC自我更新和多能性的新型基因.
- 研究转录因子PRDM14在维持多能性的特定作用及其在细胞重编程中的潜力.
主要方法:
- 在hESCs中进行全基因组RNA干扰 (RNAi) 选.
- 转录因子PRDM14的功能性研究,包括直接向基因分析.
- 全基因组位置分析 (ChIP-seq) 来评估PRDM14的相互作用.
- 获得功能测试用于体细胞重编程.
主要成果:
- 一个全基因组RNAi屏幕确定了多个参与转录调节和染色质重塑的基因,这些基因影响hESC特性.
- PRDM14通过其近位增强剂直接调节多能性基因POU5F1的表达.
- PRDM14与核心多能性因子OCT4,NANOG和SOX2共定位,表明其融入了监管网络.
- 当与OCT4,SOX2和KLF4.4相结合时,PRDM14可以提高人类纤维细胞的重编程效率.
结论:
- PRDM14是维持人类胚胎干细胞身份的关键转录因子.
- PRDM14在人类体细胞中重新获得多能性方面发挥着重要作用,突出显示了其治疗潜力.
相关概念视频
00:58Embryonic Stem Cells
Embryonic stem (ES) cells are undifferentiated pluripotent cells, meaning they can produce any cell type in the body. This gives them tremendous potential in science and medicine since they can generate specific cell types for use in research or to replace body cells lost due to damage or disease.
00:57Embryonic Stem Cells
Embryonic stem (ES) cells were first discovered in mice in 1981 by Martin Evans. In 1998, James Thomson identified a method to isolate embryonic stem cells from humans. Human embryonic stem cells (hESCs) are obtained from 3-5 day old embryos that remain unused after an in vitro fertilization procedure.
ES cells are grown in a culture medium where they can divide indefinitely, creating ES cell lines. Under certain conditions, ES cells can differentiate, either spontaneously into a variety of...
ES cells are grown in a culture medium where they can divide indefinitely, creating ES cell lines. Under certain conditions, ES cells can differentiate, either spontaneously into a variety of...
01:14Maintenance of the ES Cell State
The cells of the blastocyst inner cell mass only remain pluripotent for a short time. This state of pluripotency and self-renewal can be maintained in embryonic stem (ES) cell culture by adding specific chemicals or growth factors to ensure the cells can continue dividing and later differentiate into different cell types. In some cases, the cells are grown on a feeder layer of differentiated cells, which provides the growth factors and extracellular matrix components necessary for stem cell...