UTF1表达对于人类iPSCs的生成和维护很重要
Khyati Raina1, Kirti Modak2, Chitra Premkumar3
1Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati, Assam, India.
Stem cell reviews and reports
|January 4, 2025
概括
不分化的胚胎细胞转录因子1 (UTF1) 对于保持人类诱导多能干细胞 (iPSC) 的身份和稳定性至关重要. UTF1 枯竭会损害重编程效率和多能性,而不会导致亡.
科学领域:
- 干细胞生物学 干细胞生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 基因调节 基因调节
背景情况:
- 不分化的胚胎细胞转录因子1 (UTF1) 对胚胎发育和维持多能性至关重要.
- UTF1在多能干细胞中表达高,但其在人类诱导多能干细胞 (iPSCs) 中的作用仍未得到充分研究.
- 之前在小鼠模型中的研究强调了UTF1的重要性,需要对人类iPSC进行研究.
研究的目的:
- 研究UTF1在维持人类iPSC多能性和稳定性的作用.
- 分析UTF1耗尽对iPSC重编程效率,细胞形态和多能性标记物的影响.
- 探索UTF1下调对iPSC差异化和可行性的机制性影响.
主要方法:
- 使用CRISPR/Cas9基因编辑,在人类纤维细胞和iPSC中产生UTF1淘汰.
- 病变载体促进了UTF1淘汰纤维细胞重编程成为iPSCs.
- 西部涂抹,PCR和流细胞测量评估了多能性标记物,细胞形态和活力.
- 一个shRNA被整合到下调UTF1表达力学研究.
主要成果:
- UTF1淘汰赛显著降低了重编程效率,并增加了人类iPSC的自发分化.
- 逐渐减少UTF1导致细胞形态变化和OCT4和SOX2多能性标志物的表达减少.
- 与完全淘汰赛不同,部分UTF1下调并没有诱导亡,这表明多能性丧失独立于亡途径.
结论:
- UTF1对于保持人类iPSCs的多能性和活力至关重要.
- UTF1的枯竭会对干细胞的基本特性产生负面影响,对治疗应用构成挑战.
- 需要进一步研究UTF1控制多能性和分化的机制途径,以增强IPSC在临床使用中的稳定性.
更多相关视频
12:03Generation of Human Induced Pluripotent Stem Cells from Peripheral Blood Using the STEMCCA Lentiviral Vector
Published on: October 31, 2012
26.5K
12:10Generation of Induced Pluripotent Stem Cells by Reprogramming Human Fibroblasts with the Stemgent Human TF Lentivirus Set
Published on: December 8, 2009
29.9K
相关概念视频
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
21.8K
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...
21.8K
