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

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 decad...

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Main Authors: Viola Volpato, Caleb Webber
Format: Article
Language:English
Published: The Company of Biologists 2020-01-01
Series:Disease Models & Mechanisms
Subjects:
Online Access:http://dmm.biologists.org/content/13/1/dmm042317
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author Viola Volpato
Caleb Webber
author_facet Viola Volpato
Caleb Webber
author_sort Viola Volpato
collection DOAJ
description 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.
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spelling doaj.art-a4465fcd294b428e937a1e64ceedd66b2022-12-22T00:10:08ZengThe Company of BiologistsDisease Models & Mechanisms1754-84031754-84112020-01-0113110.1242/dmm.042317042317Addressing variability in iPSC-derived models of human disease: guidelines to promote reproducibilityViola Volpato0Caleb Webber1 UK Dementia Research Institute at Cardiff University, Division of Psychological Medicine and Clinical Neuroscience, Haydn Ellis Building, Maindy Rd, Cardiff CF24 4HQ, UK UK Dementia Research Institute at Cardiff University, Division of Psychological Medicine and Clinical Neuroscience, Haydn Ellis Building, Maindy Rd, Cardiff CF24 4HQ, UK 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.http://dmm.biologists.org/content/13/1/dmm042317bioinformaticscellular heterogeneityreproducibilityipscs
spellingShingle Viola Volpato
Caleb Webber
Addressing variability in iPSC-derived models of human disease: guidelines to promote reproducibility
Disease Models & Mechanisms
bioinformatics
cellular heterogeneity
reproducibility
ipscs
title Addressing variability in iPSC-derived models of human disease: guidelines to promote reproducibility
title_full Addressing variability in iPSC-derived models of human disease: guidelines to promote reproducibility
title_fullStr Addressing variability in iPSC-derived models of human disease: guidelines to promote reproducibility
title_full_unstemmed Addressing variability in iPSC-derived models of human disease: guidelines to promote reproducibility
title_short Addressing variability in iPSC-derived models of human disease: guidelines to promote reproducibility
title_sort addressing variability in ipsc derived models of human disease guidelines to promote reproducibility
topic bioinformatics
cellular heterogeneity
reproducibility
ipscs
url http://dmm.biologists.org/content/13/1/dmm042317
work_keys_str_mv AT violavolpato addressingvariabilityinipscderivedmodelsofhumandiseaseguidelinestopromotereproducibility
AT calebwebber addressingvariabilityinipscderivedmodelsofhumandiseaseguidelinestopromotereproducibility