转录因子E4F1通过调节线粒体功能和细胞周期进展来决定精子干细胞命运的决定
Rong-Ge Yan1,2, Zhen He1,2, Fei-Chen Wang1,2
1Key Laboratory of Adaptation and Evolution of Plateau Biota, Northwest Plateau Institute of Biology, Chinese Academy of Sciences, Xining, 810001, China.
Cell & bioscience
|September 25, 2023
概括
转录因子E4F1对于通过调节线粒体功能和新陈代谢来维持小鼠精子干细胞 (SSC) 是必不可少的. 失去E4F1导致SSC损失,影响精子生成.
科学领域:
- 生殖生物学 生殖生物学
- 干细胞生物学 干细胞生物学
- 代谢调节 代谢调节 代谢调节 代谢调节
背景情况:
- 精子干细胞 (SSC) 对于哺乳动物的持续精子生成至关重要,需要自我更新和分化.
- 代谢显著影响干细胞命运,但其在SSC发育和维护中的作用尚未完全理解.
研究的目的:
- 为了确定调节SSC命运的转录因子.
- 研究转录因子E4F1在SSC维护和新陈代谢中的作用.
主要方法:
- 单细胞色素可访问性分析以确定转录因子调节者.
- 在小鼠生殖细胞中条件删除E4F1.
- 单细胞RNA测序以分析基因表达变化.
- 评估线粒体形态和脂肪酸代谢.
主要成果:
- 确定了37种SSC命运的潜在转录因子调节剂.
- 在小鼠生殖细胞中E4F1的条件删除导致了不分化精子的逐渐丧失.
- E4F1是线粒体功能的关键调节剂,与呼吸链中的基因结合.
- 失去E4F1导致线粒体形态异常,脂肪酸代谢受损,细胞循环停止和亡.
- 在缺乏E4f1的细胞中,p53删除仅暂时挽救了精子的损失.
结论:
- 代谢信号对于干细胞命运决定至关重要.
- 在哺乳动物中,E4F1在调节新陈代谢和维持SSC命运方面发挥着至关重要的作用.
- 通过E4F1介导的转录程序对于SSC维护至关重要.
相关概念视频
Spermatogenesis
102.6K
Spermatogenesis is the process by which haploid sperm cells are produced in the male testes. It starts with stem cells located close to the outer rim of seminiferous tubules. These spermatogonial stem cells divide asymmetrically to give rise to additional stem cells (meaning that these structures “self-renew”), as well as sperm progenitors, called spermatocytes. Importantly, this method of asymmetric mitotic division maintains a population of spermatogonial stem cells in the male...
102.6K
Methods of Nuclear Reprogramming
1.8K
Nuclear reprogramming is a process of transforming one cell type into an unrelated cell type by epigenetic changes that alter the cell’s original gene expression pattern. Such epigenetic changes force cells to express a different set of genes, which play a significant role in inducing transformation into other cell types. Nuclear reprogramming offers applications in reproductive cloning for livestock propagation and regenerative medicine — developing patient-specific cells for...
1.8K
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
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
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
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


