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Addressing variability in iPSC-derived models of human disease: guidelines to promote reproducibility

Volpato, Viola and Webber, Caleb ORCID: 2020. Addressing variability in iPSC-derived models of human disease: guidelines to promote reproducibility. Disease Models and Mechanisms 13 (1) , dmm042317. 10.1242/dmm.042317

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Induced pluripotent stem cell (iPSC) technologies have provided in vitro models of inaccessible human cell types, yielding new insights into disease mechanisms especially for neurological disorders. However, without due consideration, the thousands of new human iPSC lines generated in the past decade will inevitably affect the reproducibility of iPSC-based experiments. Differences between donor individuals, genetic stability and experimental variability contribute to iPSC model variation by impacting differentiation potency, cellular heterogeneity, morphology, and transcript and protein abundance. Such effects will confound reproducible disease modelling in the absence of appropriate strategies. In this Review, we explore the causes and effects of iPSC heterogeneity, and propose approaches to detect and account for experimental variation between studies, or even exploit it for deeper biological insight.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Publisher: Company of Biologists: OAJ
ISSN: 1754-8403
Date of First Compliant Deposit: 30 January 2020
Date of Acceptance: 10 December 2019
Last Modified: 27 Jul 2023 16:41

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