埃弗林向前信号控制多能干细胞中的物种间细胞竞争
bioRxiv : the preprint server for biology
|June 19, 2024
概括
鼠标细胞通过以林A-EPHA相互作用在物种间嵌合体形成过程中向人类细胞发出死亡信号. 阻止这种相互作用有助于人类多能干细胞的生存和嵌合体的发展.
科学领域:
- 发展生物学 发展生物学
- 细胞生物学 细胞生物学
- 再生医学是一种再生医学.
背景情况:
- 细胞竞争是一种在发育过程中消除不适合细胞的进化保存机制.
- 跨物种的嵌合体形成包括与宿主细胞接触后的供体细胞的亡,但信号机制尚不清楚.
研究的目的:
- 研究小鼠和人类多能干细胞 (PSC) 之间的细胞竞争机制.
- 确定在物种间相互作用期间负责异源细胞死亡的信号通路.
主要方法:
- 开发一种跨物种细胞接触报告系统.
- 单细胞RNA测序 (scRNA-seq) 分析共同培养的小鼠和人类PSCs.
- 药理和遗传抑制已识别的信号通路.
主要成果:
- 鼠标细胞上的以林A配体向表达EPHA受体的人类细胞信号细胞死亡.
- 阻断以林A-EPHA相互作用可以提高人类PSC的存活率,并促进体外和体内嵌合体的形成.
- 对Ephrin前向信号的遗传抑制也改善了人类PSC的存活率.
结论:
- 埃弗林A-EPHA信号传递是调解物种间PSC竞争的关键机制.
- 针对这种途径可以增强动物人性化组织和器官的生成.
- 这些发现为再生医学应用提供了新的策略.
相关概念视频
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
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
Chromatin Modification in iPS Cells
1.6K
Chromatin modification alters gene expression; therefore, scientists can add histone-modifying enzymes, histone variants, and chromatin remodeling complexes to somatic cells to aid reprogramming into pluripotent stem (iPS) cells.
Compact chromatin makes reprogramming difficult. Enzymes, such as histone demethylases and acetyltransferases, are often added during reprogramming to loosen the chromatin, making the DNA more accessible to transcription factors. Molecules that inhibit histone...
Compact chromatin makes reprogramming difficult. Enzymes, such as histone demethylases and acetyltransferases, are often added during reprogramming to loosen the chromatin, making the DNA more accessible to transcription factors. Molecules that inhibit histone...
1.6K
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
Induced Pluripotent Stem Cells
22.5K
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...
22.5K


