Kochurani K J, Suganya Annie A, Nair Madhumathy G, Louis Jiss Maria, Majumder Aditi, Kumar Santhosh K, Abraham Parvin, Dutta Debasree, Maliekal Tessy T
Cancer Research Program, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, Kerala, India, 695014.
Chemical Biology Group, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, Kerala, India, 695014.
Sci Rep. 2015 Nov 24;5:17218. doi: 10.1038/srep17218.
Flow cytometry is a reliable method for identification and purification of live cells from a heterogeneous population. Since permeabilized cells cannot be sorted live in a FACS sorter, its application in isolation of functional cells largely depends on antibodies for surface markers. In various fields of biology we find intracellular markers that reveal subpopulations of biological significance. Cell cycle stage specific molecules, metastatic signature molecules, stemness associated proteins etc. are examples of potential markers that could improve the research and therapy enormously. Currently their use is restricted by lack of techniques that allow live detection. Even though a few methods like aptamers, droplet-based microfluidics and smartflares are reported, their application is limited. Here, for the first time we report a simple, cost-effective and efficient method of live sorting of cells based on the expression of an intracellular marker using a fluorophore-tagged binding peptide. The target molecule selected was a histone chaperone, HIRA, the expression of which can predict the fate of differentiating myoblast. Our results confirm that the peptide shows specific interaction with its target; and it can be used to separate cells with differential expression of HIRA. Further, this method offers high purity and viability for the isolated cells.
流式细胞术是从异质群体中鉴定和纯化活细胞的可靠方法。由于通透化的细胞不能在荧光激活细胞分选仪中进行活细胞分选,其在功能细胞分离中的应用很大程度上依赖于针对表面标志物的抗体。在生物学的各个领域,我们都发现了揭示具有生物学意义的亚群的细胞内标志物。细胞周期阶段特异性分子、转移特征分子、干性相关蛋白等都是可能极大地改善研究和治疗的潜在标志物的例子。目前,它们的使用受到缺乏允许活细胞检测技术的限制。尽管报道了一些方法,如适体、基于液滴的微流控技术和智能荧光探针,但它们的应用有限。在此,我们首次报道了一种基于使用荧光团标记的结合肽对细胞内标志物的表达进行活细胞分选的简单、经济高效的方法。选择的靶分子是一种组蛋白伴侣HIRA,其表达可以预测成肌细胞分化的命运。我们的结果证实该肽与其靶标表现出特异性相互作用;并且它可用于分离具有不同HIRA表达的细胞。此外,该方法为分离的细胞提供了高纯度和活力。