单细胞转录组分析揭示了精子干细胞命运过渡的关键调节者
Shuang Li1,2,3, Rong-Ge Yan1,2, Xue Gao1,2
1Key Laboratory of Adaptation and Evolution of Plateau Biota, Northwest Institute of Plateau Biology, Chinese Academy of Sciences, Qinghai, 810008, China.
BMC genomics
|February 3, 2024
概括
研究人员确定了表达Eomes的精子干细胞 (SSC) 作为生殖线再生至关重要的静止人群. 删除Eomes增强了SSC再生,揭示了它在干细胞命运中的作用.
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
- 遗传学 是一个遗传学.
背景情况:
- 精子干细胞 (SSC) 对于哺乳动物的持续精子生产和生殖线再生至关重要.
- 精确的SSC及其祖先的分子身份尚未完全理解.
研究的目的:
- 通过单细胞转录组分析,破译控制SSC命运过渡的分子签名.
- 确定调节SSC命运决定和祖先状态的关键转录因子.
主要方法:
- 单细胞转录组分析孤立的小鼠不分化的精子.
- 特定的精子子亚型的表征,包括表达eomes的细胞.
- 条件基因删除和强制表达研究,以评估基因功能 in vivo.
主要成果:
- 确定了一个静止的SSC亚群 (A单个),以Eomes表达标记,为可移植的SSC进行丰富.
- 条件删除Eomes增强了受伤后的SSC再生,而不会影响稳定状态的精子生成.
- 强迫Eomes表达通过影响未分化的精子细胞循环进展来破坏精子生成.
- Eomes+细胞显示出不同的子集,以及糖解/葡萄糖生成和PI3/Akt信号在再生中的参与.
结论:
- 描述了一个静止的SSC亚群,Eomes+spermatogonia,对生殖线再生至关重要.
- 提供了SSC命运决定的动态转录地图,并确定了Eomes作为一个关键的调节器.
相关概念视频
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
Combinatorial Gene Control
8.3K
Combinatorial gene control is the synergistic action of several transcriptional factors to regulate the expression of a single gene. The absence of one or more of these factors may lead to a significant difference in the level of gene expression or repression.
The expression of more than 30,000 genes is controlled by approximately 2000-3000 transcription factors. This is possible because a single transcription factor can recognize more than one regulatory sequence. The specificity in gene...
The expression of more than 30,000 genes is controlled by approximately 2000-3000 transcription factors. This is possible because a single transcription factor can recognize more than one regulatory sequence. The specificity in gene...
8.3K
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
Regulation of Expression at Multiple Steps
910
The gene expression in cells is regulated at different stages: (i) transcription, (ii) RNA processing, (iii) RNA localization, and (iv) translation. Transcriptional regulation is mediated by regulatory proteins such as transcription factors, activators, or repressors—these control gene expression by initiating or inhibiting the transcription of genes. Once a precursor or pre-mRNA is produced, it undergoes post-transcriptional modification, including 5' capping, splicing, and the...
910


