ETV2过度表达促进了多能干细胞到内皮细胞的有效分化
Yunfeng Ding1, Soniya Tamhankar1, Feifan Du1
1Department of Chemical and Biological Engineering, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Biotechnology and bioengineering
|March 26, 2025
概括
我们开发了一种快速的方法,使用ETV2基因诱导从人类多能干细胞 (hPSCs) 制造纯内皮细胞 (ECs). 这种技术只需5天就能产生99%纯度的EC,加速了研究和应用.
科学领域:
- 干细胞生物学 干细胞生物学
- 血管生物学 血管生物学
- 细胞分化的细胞分化.
背景情况:
- 内皮细胞 (ECs) 对于血管功能至关重要.
- 传统的EC与人类多能干细胞 (hPSC) 的差异化需要很长时间 (2周) 并需要优化.
- ETV2是诱导内皮细胞命运的关键转录因子.
研究的目的:
- 开发一种更快,更有效的方法,从hPSC中产生纯的EC.
- 为了利用ETV2的过度表达,快速实现EC差异化.
- 为研究应用建立可扩展的EC源.
主要方法:
- 在hPSC中过度表达转录因子ETV2,从而产生可诱导的ETV2-hPSC.
- 一个两阶段的分化策略:第一阶段 (基底诱导介质) 和第二阶段 (内皮介质).
- 优化播种密度和媒介组成.
主要成果:
- 在没有进行细胞分类的情况下,在5天内获得99%纯CD31+CD144+ECs (iETV2-ECs).
- 在iETV2-ECs中证明了体外血管生成,LDL吸收和细胞因子反应.
- 转录组分析显示,基因表达特征与传统衍生ECs相似.
- iETV2-ECs可能会在对特定信号调节器的反应中获得大脑EC表型.
结论:
- 以ETV2为媒介的差异化提供了一种快速有效的方法,可以从hPSC中生成高纯度的EC.
- 这种可扩展的EC源对诸如血脑屏障建模等应用具有前景.
- 优化的协议显著减少了差异化时间和复杂性.
更多相关视频
相关概念视频
iPS Cell Differentiation
2.7K
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.
2.7K
Induced Pluripotent Stem Cells
21.9K
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...
21.9K
Maintenance of the ES Cell State
2.2K
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...
2.2K
Embryonic Stem Cells
3.4K
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...
3.4K
Regulation of Angiogenesis and Blood Supply
2.5K
Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits. Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
2.5K


