内生VEGF信号传递作为人类原始多能性的守护者
Xu Wu1, Chunsheng Wen2, Chaonan Zhu1
1Department of Histoembryology, Genetics and Developmental Biology, Shanghai Key Laboratory of Reproductive Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Nature communications
|March 13, 2026
概括
内生血管内皮生长因子 (VEGF) 信号传递对于维持人类胚胎干细胞 (hESC) 多能性至关重要. 抑制VEGF信号发送会触发分化成类似于热囊细胞的细胞.
科学领域:
- 干细胞生物学 干细胞生物学
- 发育生物学是发展生物学.
- 分子信号传递是分子信号传递.
背景情况:
- 人类胚胎干细胞 (hESCs) 的自我更新和多能性取决于信号通路.
- 内源性多能性途径的理解比外源性途径要少.
研究的目的:
- 调查内源性血管内皮生长因子 (VEGF) 信号在维持原始hESC多能性的作用.
- 阐明VEGF在hESC中的功能背后的分子机制.
主要方法:
- 在原始化,原始化和差异化hESC中研究了VEGF信号活动.
- 使用药理学VEGFR抑制,可溶性诱受体 (sFLT1/sKDR) 和CRISPR介导的VEGFR1/2淘汰.
- 分析了对BMP通路和NANOG表达的下游影响.
- 使用BMP抑制和NANOG过度表达评估了救援效应.
主要成果:
- 在原始化hESC中,VEGF信号是活跃的,在原始细胞中是静止的,在分化时是不活跃的.
- 在原始化hESC中抑制VEGFR导致自我更新受损,并诱导类似于热囊细胞的分化.
- 抑制VEGFR激活了BMP通路并降低了NANOG水平.
- 纳诺直接抑制BMP组件和热囊细胞基因.
结论:
- 内生VEGF信号传递对于维持原始hESC多能性至关重要.
- 涉及BMP和NANOG的VEGF依赖网络规范了多能性和血统承诺.
- 研究结果通过信号级联和转录因子提供了对综合调节的见解.
相关概念视频
01:24Regulation of Angiogenesis and Blood Supply
3.9K
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...
3.9K
01:14Maintenance of the ES Cell State
2.8K
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...
2.8K
01:13Induced Pluripotent Stem Cells
28.4K
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...
28.4K
01:13Induced Pluripotent Stem Cells
4.0K
4.0K
01:06Induced Pluripotent Stem Cells
5.9K
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...
Somatic...
5.9K
01:29Somatic to iPS Cell Reprogramming
2.8K
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...
2.8K