Institute of Biotechnology, Ferdowsi University of Mashhad, Mashhad, Iran.
Biochem Biophys Res Commun. 2009 Dec 25;390(4):1106-10. doi: 10.1016/j.bbrc.2009.10.038. Epub 2009 Oct 13.
RNA interference (RNAi) is a post-transcriptional conserved mechanism, which is present in a wide range of organisms and leads to specific gene silencing. The effector molecules in this process are double-stranded RNAs (dsRNAs) that are homologous in sequence to the silenced gene and are processed into small interfering RNAs (siRNAs) by an enzyme called Dicer. Consequently, siRNAs are incorporated into an RNA-induced silencing complex, which finds and cleaves the target mRNA. Because of its exquisite specificity and efficiency, RNAi is being considered as an important tool for gene silencing in living organisms. Human embryonic stem cells (HESCs) have the ability to both self-renew and differentiate into cell types of all three germ layers. HESCs open new avenues for understanding some of the very early lineage determination events that occur during embryogenesis and are also considered as an important source of cells for cell replacement therapies. Understanding how the signaling pathways orchestrate and direct HESC differentiation toward certain cell types is critical for basic research. In this way RNAi appears to be a valuable tool in stem cell biology for dissecting the pathways involved in differentiation, lineage segregation and production of cells for cell therapy. Here, we review the prospects of combining RNAi and HESC manipulation for both basic research and future therapies.
RNA 干扰 (RNAi) 是一种转录后保守机制，存在于广泛的生物体中，导致特定基因沉默。该过程中的效应分子是双链 RNA (dsRNA)，其序列与被沉默的基因同源，并被一种称为 Dicer 的酶加工成小干扰 RNA (siRNA)。因此，siRNA 被整合到 RNA 诱导的沉默复合物中，该复合物找到并切割靶 mRNA。由于其高度特异性和效率，RNAi 被认为是生物体中基因沉默的重要工具。人类胚胎干细胞 (HESC) 具有自我更新和分化为所有三个胚层细胞类型的能力。HESC 为理解胚胎发生过程中发生的一些非常早期的谱系决定事件开辟了新的途径，也被认为是细胞替代疗法的重要细胞来源。了解信号通路如何协调和指导 HESC 向特定细胞类型分化对于基础研究至关重要。在这种情况下，RNAi 似乎是干细胞生物学中一种有价值的工具，可用于剖析分化、谱系分离和细胞治疗所需细胞产生过程中涉及的途径。在这里，我们综述了将 RNAi 与 HESC 操作相结合用于基础研究和未来治疗的前景。
