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Adv Exp Med Biol. 2019;1123:71-94. doi: 10.1007/978-3-030-11096-3_6.

Pluripotent Stem Cell Heterogeneity.

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iPS Cell Advanced Characterization and Development Team, Bioresource Research Center, RIKEN, Ibaraki, Japan.
Department of Bioengineering, Nagaoka University of Technology, Nagaoka, Niigata, Japan.
Department of Science of Technology Innovation, Nagaoka University of Technology, Nagaoka, Niigata, Japan.
Laboratory of Stem Cell Cultures, National institutes of Biomedical Innovation, Health and Nutrition, Osaka, Ibaraki-City, Japan.


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.


Embryonic stem cells (ESCs); Human embryonic stem cells (hESCs); Human pluripotent stem cells (hPSCs); Human pluripotent stem cells (hiPSCs); Induced pluripotent stem cells (iPSCs); Pluripotent stem cells (PSCs)

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