雅克活性通过控制MESP1表达来调节中皮细胞命运
Su Yao1, Yalin Zhu1, Fenglian He1
1Institute for Regenerative Medicine, State Key Laboratory of Cardiology and Medical Innovation Center, Shanghai East Hospital, Shanghai Key Laboratory of Signaling and Disease Research, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China.
European journal of cell biology
|August 25, 2024
概括
研究人员确定了JAK抑制剂CYT387,作为中皮细胞中MESP1表达的强有力的激活剂. 这一发现增强了对心脏发育和中皮细胞命运调节的理解.
科学领域:
- 发展生物学 发展生物学
- 干细胞生物学 干细胞生物学
- 分子心脏病学分子心脏病学
背景情况:
- 精确的基因表达对于心脏发育至关重要,由信号通路和转录因子指导.
- MESP1是对心脏发育至关重要的关键转录因子,但其调节机制尚不清楚.
- 了解MESP1调节对于推进心脏再生医学至关重要.
研究的目的:
- 为了确定中皮细胞中MESP1表达的新型调节者.
- 研究JAK信号在早期中皮体发育和MESP1转录中的作用.
- 探索已识别的调节剂在促进心肌细胞分化方面的潜力.
主要方法:
- 开发了一种使用人类多能干细胞 (hPSCs) 分化为中皮细胞的高含量屏试验.
- 在屏幕上使用了JAK1/JAK2激酶抑制剂CYT387.
- 进行了涉及度和WNT信号通路分析的机械学研究.
主要成果:
- 鉴定出CYT387是中皮细胞中MESP1表达的强有力的激活剂.
- 证明CYT387在体外促进心肌细胞分化.
- 从机制上讲,JAK抑制通过减少细胞质和激活WNT信号来增强MESP1的表达.
结论:
- 在早期的中皮细胞中,JAK信号传递起着重要作用.
- 建立了JAK-STAT路径和MESP1转录调节之间的联系.
- 提供了对调节中皮和心脏发育的分子机制的新见解.
相关概念视频
The JAK-STAT Signaling Pathway
8.7K
Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as SH2...
8.7K
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
Role Of Notch Signalling In Intestinal Stem Cell Renewal
2.1K
Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
2.1K
Abnormal Proliferation
4.5K
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.5K
Hedgehog Signaling Pathway
7.3K
The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...
7.3K


