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转录因子介导的重编程为多能性。

Transcriptional Factors Mediated Reprogramming to Pluripotency.

机构信息

Laboratory Animal Center, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, 710061, China.

Institute of Advanced Studies, Shenzhen University, Shenzhen, 518060, China.

出版信息

Curr Stem Cell Res Ther. 2024;19(3):367-388. doi: 10.2174/1574888X18666230417084518.

Abstract

A unique kind of pluripotent cell, i.e., Induced pluripotent stem cells (iPSCs), now being targeted for iPSC synthesis, are produced by reprogramming animal and human differentiated cells (with no change in genetic makeup for the sake of high efficacy iPSCs formation). The conversion of specific cells to iPSCs has revolutionized stem cell research by making pluripotent cells more controllable for regenerative therapy. For the past 15 years, somatic cell reprogramming to pluripotency with force expression of specified factors has been a fascinating field of biomedical study. For that technological primary viewpoint reprogramming method, a cocktail of four transcription factors (TF) has required: Kruppel-like factor 4 (KLF4), four-octamer binding protein 34 (OCT3/4), MYC and SOX2 (together referred to as OSKM) and host cells. IPS cells have great potential for future tissue replacement treatments because of their ability to self-renew and specialize in all adult cell types, although factor-mediated reprogramming mechanisms are still poorly understood medically. This technique has dramatically improved performance and efficiency, making it more useful in drug discovery, disease remodeling, and regenerative medicine. Moreover, in these four TF cocktails, more than 30 reprogramming combinations were proposed, but for reprogramming effectiveness, only a few numbers have been demonstrated for the somatic cells of humans and mice. Stoichiometry, a combination of reprogramming agents and chromatin remodeling compounds, impacts kinetics, quality, and efficiency in stem cell research.

摘要

一种独特的多能细胞,即诱导多能干细胞(iPSCs),现在正被作为 iPSC 合成的目标,是通过重编程动物和人类分化细胞(为了高效形成 iPSCs,不改变遗传组成)产生的。特定细胞向 iPSC 的转化通过使多能细胞更易于控制来为再生治疗提供了可能,从而彻底改变了干细胞研究。在过去的 15 年中,通过强制表达特定因子将体细胞重编程为多能性一直是生物医学研究的一个迷人领域。对于这种技术主要观点的重编程方法,需要使用四种转录因子(TF)的鸡尾酒:Kruppel 样因子 4(KLF4)、四聚体结合蛋白 34(OCT3/4)、MYC 和 SOX2(统称为 OSKM)和宿主细胞。由于 IPS 细胞能够自我更新并专门分化为所有成年细胞类型,因此它们在未来的组织替代治疗中有很大的潜力,尽管因子介导的重编程机制在医学上仍未得到很好的理解。这项技术大大提高了性能和效率,使其在药物发现、疾病建模和再生医学中更加有用。此外,在这四种 TF 鸡尾酒中,提出了超过 30 种重编程组合,但就重编程效果而言,只有少数组合被证明对人类和小鼠的体细胞有效。化学计量学,即重编程剂和染色质重塑化合物的组合,会影响干细胞研究中的动力学、质量和效率。

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