Department of Molecular Systems Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.
Stem Cell Rev Rep. 2012 Dec;8(4):1138-54. doi: 10.1007/s12015-012-9400-9.
Embryonic stem cells (ESCs) are capable of unlimited self-renewal while maintaining pluripotency. They are of great interest in regenerative medicine due to their ability to differentiate into all cell types of the three embryonic germ layers. Recently, induced pluripotent stem cells (iPSCs) have shown similarities to ESCs and thus promise great therapeutic potential in regenerative medicine. Despite progress in stem cell biology, our understanding of the exact mechanisms by which pluripotency and self-renewal are established and maintained is largely unknown. A better understanding of these processes may lead to discovery of alternative ways for reprogramming, differentiation and more reliable applications of stem cells in therapies. It has become evident that proteins generally function as members of large complexes that are part of a more complex network. Therefore, the identification of protein-protein interactions (PPI) is an efficient strategy for understanding protein function and regulation. Systematic genome-wide and pathway-specific PPI analysis of ESCs has generated a network of ESC proteins, including major transcription factors. These PPI networks of ESCs may contribute to a mechanistic understanding of self-renewal and pluripotency. In this review we describe different experimental approaches for the identification of PPIs along with various databases. We discuss biological findings and technical challenges encountered with interactome studies of pluripotent stem cells, and provide insight into how interactomics is likely to develop.
胚胎干细胞(ESCs)具有无限自我更新的能力,同时保持多能性。由于它们能够分化为三个胚胎胚层的所有细胞类型,因此在再生医学中引起了极大的兴趣。最近,诱导多能干细胞(iPSCs)显示出与 ESCs 的相似性,因此在再生医学中具有巨大的治疗潜力。尽管在干细胞生物学方面取得了进展,但我们对多能性和自我更新的确切建立和维持机制的理解在很大程度上仍是未知的。更好地了解这些过程可能会发现替代的重编程、分化方法,以及更可靠地将干细胞应用于治疗。显然,蛋白质通常作为大复合物的成员发挥作用,而这些复合物是更复杂网络的一部分。因此,鉴定蛋白质-蛋白质相互作用(PPI)是理解蛋白质功能和调节的有效策略。对 ESCs 的全基因组系统和特定途径的 PPI 分析生成了 ESCs 蛋白质网络,包括主要转录因子。这些 ESCs 的 PPI 网络可能有助于理解自我更新和多能性的机制。在这篇综述中,我们描述了鉴定 PPI 的不同实验方法以及各种数据库。我们讨论了多能干细胞相互作用组研究中遇到的生物学发现和技术挑战,并深入了解了相互作用组学可能的发展方向。