iPS Cell Advanced Characterization and Development Team, Bioresource Research Center, RIKEN, Ibaraki, Japan.
Department of Bioengineering, Nagaoka University of Technology, Nagaoka, Niigata, Japan.
Adv Exp Med Biol. 2019;1123:71-94. doi: 10.1007/978-3-030-11096-3_6.
Pluripotent stem cells (PSCs), including embryonic stem cells and induced pluripotent stem cells, show heterogeneity with respect to their pluripotency, self-renewal ability, and other traits. PSC heterogeneity may exist among cell lines, among cells within a line, and among temporal states of individual cells. Both genetic and epigenetic factors can cause heterogeneity among cell lines. Heterogeneity among cells within a cell line may arise during long-term culturing even when a PSC cell line is derived from a single cell. Moreover, the expression levels of genes and proteins in PSCs fluctuate continuously at a frequency ranging from a few hours to a few days. Such heterogeneity decreases the reproducibility of research. Thus, methods related to the detection, reduction, and control of heterogeneity in experiments involving human PSCs need to be developed. Further, the presupposition that PSCs are highly heterogeneous should be taken into account by all researchers not only when they plan their own studies but also when they review the studies of other researchers in this field.
多能干细胞（PSCs），包括胚胎干细胞和诱导多能干细胞，在其多能性、自我更新能力和其他特性方面表现出异质性。PSC 异质性可能存在于细胞系之间、细胞系内的细胞之间以及单个细胞的时间状态之间。遗传和表观遗传因素都可能导致细胞系之间的异质性。即使 PSC 细胞系是从单个细胞中衍生出来的，细胞系内的细胞之间的异质性也可能在长期培养过程中出现。此外，PSCs 中的基因和蛋白质的表达水平在几小时到几天的频率范围内持续波动。这种异质性降低了研究的可重复性。因此，需要开发与人类 PSCs 实验中的异质性检测、减少和控制相关的方法。此外，所有研究人员在计划自己的研究时，不仅在审查该领域其他研究人员的研究时，都应该考虑到 PSCs 高度异质性的假设。
