先驱因素ETV2通过招募抑制器REST来保护内皮细胞特异性,以限制替代血统承诺
Danyang Chen1, Xiaonuo Fan1, Ninghe Sun2,3
1Department of Cardiology, Boston Children's Hospital, Boston, MA, USA.
Nature cardiovascular research
|June 10, 2025
概括
干细胞中的ETV2过度表达通过激活EC基因和招募REST来阻止其他细胞命运,驱动内皮细胞 (EC) 规范. 这揭示了再生医学的关键机制.
科学领域:
- 发展生物学 发展生物学
- 再生医学是一种再生医学.
- 干细胞生物学 干细胞生物学
背景情况:
- 细胞命运规范对于发展和再生医学至关重要.
- ETV2是已知的内皮细胞 (EC) 谱系规范的主调节器.
研究的目的:
- 调查ETV2过度表达从人类诱导的多能干细胞衍生中皮细胞原始体中指定EC的分子机制.
- 确定ETV2的开拓性活动的范围,并确定其直接下游目标.
主要方法:
- 电影下染色体的裂变 (CUT&RUN) 的方法
- 单细胞RNA测序 (scRNA-seq) 是一种
- 单细胞测试用于转移酶可访问的染色体测序 (scATAC-seq)
- 功能查是指功能查.
- 候选人的验证 候选人的验证
主要成果:
- ETV2过度表达有效地指定了EC和抑制了替代细胞命运.
- 确定了ETV2.2的直接下游目标基因.
- 发现了EC规范的重要辅助因子,包括GABPA和REST.
- ETV2招募抑制器REST来抑制非EC血统基因.
结论:
- ETV2作为一个先驱因素,不仅激活了EC特定的基因,而且还招募了像REST这样的抑制剂来阻止替代血统的承诺.
- 提供了EC规范的高分辨率分子理解.
- 突出了先驱因素在细胞命运决定中的双重作用.
相关概念视频
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
RNA Polymerase II Accessory Proteins
9.1K
Proteins that regulate transcription can do so either via direct contact with RNA Polymerase or through indirect interactions facilitated by adaptors, mediators, histone-modifying proteins, and nucleosome remodelers. Direct interactions to activate transcription is seen in bacteria as well as in some eukaryotic genes. In these cases, upstream activation sequences are adjacent to the promoters, and the activator proteins interact directly with the transcriptional machinery. For example, in...
9.1K
Master Transcription Regulators
6.9K
Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
6.9K
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
Somatic to iPS Cell Reprogramming
2.2K
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...
2.2K
Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal
2.2K
Erythropoietin-producing hepatocellular carcinoma receptor (Eph) and its ligand, Eph receptor-interacting protein (Ephrin) were first discovered in the human carcinoma cell line, hence the name. Ephrin-Eph interaction guides cells to reach their appropriate location in adult tissues. They also play an essential role in the immune system by helping in immune cell migration, adhesion, and activation. Based on their structure and function, Eph is divided into two classes — EphA and EphB.
2.2K


