Systematic assessment of variability in the proteome of iPSC derivatives

Stephanie D. Beekhuis-Hoekstra, Kyoko Watanabe, Josefin Werme, Christiaan A. de Leeuw, Iryna Paliukhovich, Ka Wan Li, Frank Koopmans, August B. Smit, Danielle Posthuma*, Vivi M. Heine

*Corresponding author for this work

Research output: Contribution to JournalArticleAcademicpeer-review


The use of induced pluripotent stem cells (iPSC) to model human complex diseases is gaining popularity as it allows investigation of human cells that are otherwise sparsely available. However, due to its laborious and cost intensive nature, iPSC research is often plagued by limited sample size and putative large variability between clones, decreasing statistical power for detecting experimental effects. Here, we investigate the source and magnitude of variability in the proteome of parallel differentiated astrocytes using mass spectrometry. We compare three possible sources of variability: inter-donor variability, inter- and intra-clonal variability, at different stages of maturation. We show that the interclonal variability is significantly smaller than the inter-donor variability, and that including more donors has a much larger influence on statistical power than adding more clones per donor. Our results provide insight into the sources of variability at protein level between iPSC samples derived in parallel and will aid in optimizing iPSC studies.

Original languageEnglish
Article number102512
JournalStem Cell Research
Publication statusPublished - Oct 2021

Bibliographical note

Funding Information:
This work was funded by The Netherlands Organization for Scientific Research (NWO VICI 453-14-005). We thank Patrick Sullivan for providing us with two control lines from The Sweden Schizophrenia Study. The Sweden Schizophrenia Study was supported by the Swedish Research Council and US NIMH (awards D0886501 and MH077139 to PF Sullivan). We also thank Dr. Rachel M. Brouwer for the tSNE plot.

Publisher Copyright:
© 2021 The Author(s)

Copyright 2021 Elsevier B.V., All rights reserved.


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