作为创始转录因子,Tcf21在指定Foxd1细胞中的Juxtaglomerular细胞谱系中的创始转录因子
bioRxiv : the preprint server for biology
|April 8, 2024
概括
转录因子TCF21对于脏发育至关重要,指导Foxd1+原始细胞成为分泌蛋白的柔合体细胞. 它的表达在发育早期最高,对于细胞命运规范至关重要.
科学领域:
- 发展生物学 发展生物学
- 脏生理学 脏生理学
- 分子遗传学 分子遗传学
背景情况:
- 列宁对血压和电解质平衡至关重要,由源自Foxd1+ stromal祖先的柔合细胞 (JG) 生产.
- 引导这些原始细胞进入氨酸分泌细胞命运的具体因素在很大程度上是未知的.
- Tcf21是一种基本的螺旋环-螺旋环转录因子,因其在发育中的重要性而得到认可.
研究的目的:
- 研究转录因子Tcf21在Foxd1+原始细胞分化成JG细胞中的作用.
- 阐明在JG细胞系发展过程中Tcf21的时间动态和必要性.
- 了解JG细胞分化和脏发育背后的分子机制.
主要方法:
- 使用复合小鼠模型 (Foxd1;Tcf21和Ren1;Tcf21) 来研究Tcf21的功能.
- 采用免疫染色和现场杂交来评估蛋白表达和形态.
- 在Foxd1;Rosa26控制脏的GFP+细胞上进行了集成单细胞RNA测序 (scRNA-seq) 和scATAC-seq,以分析Tcf21表达动态.
主要成果:
- 在Foxd1+原始体中TCF21无活化导致素阳性区域减少,并改变了 afferent arteriole 形态.
- Tcf21对于表达氨酸的细胞的出现至关重要,但一旦确定氨酸细胞的身份,就不再需要它了.
- scRNA-seq和scATAC-seq揭示了Tcf21表达峰值在早期的甲膜介质细胞/细胞 (E12) 中,并在JG细胞成熟期间下降.
结论:
- 在发育过程中,Tcf21在Foxd1+细胞早期分化为JG细胞中发挥着关键作用.
- Tcf21对于表达氨酸的JG细胞的特异性至关重要,影响动脉发育.
- 这项研究强调了TCF21在脏早期发育和JG细胞系确定中的关键作用.
相关概念视频
General Transcription Factors
5.3K
Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
5.3K
TGF - β Signaling Pathway
7.3K
The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
7.3K
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
Transcription Factors
75.8K
Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
75.8K
Lineage Commitment
3.0K
Commitment is the process whereby stem cells:
3.0K
Notch Signaling Pathway
4.3K
The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not...
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not...
4.3K


