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Plating human iPSC lines on micropatterned substrates reveals role for ITGB1 nsSNV in endoderm formation

Research output: Contribution to journal › Article › peer-review

Alice Vickers, Mukul Tewary, Anna Laddach, Martina Poletti, Vasiliki Salameti, Franca Fraternali, Davide Danovi, Fiona M Watt

Original languageEnglish
Pages (from-to)2628-2641
Number of pages14
JournalStem cell reports
Volume16
Issue number11
Early online date9 Oct 2021
DOIs
E-pub ahead of print9 Oct 2021
Published9 Nov 2021
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Bibliographical note

Funding Information: We are grateful to everyone in CSCRM who provided advice and reagents. We thank Alessandra Vigilante and Chi Fung Joseph Ng for support with data analysis, and James Williams, Ruta Meleckyte, and Ana-Maria Cjuba for experimental assistance. This work was supported by grants to F.M.W. from the UK Medical Research Council (MR/PO18823/1) and the Wellcome Trust (206439/Z/17/Z; 098503/Z/12/Z). A.V. gratefully acknowledges funding from the UK Medical Research Council through the King's College London MRC Doctoral Training Partnership in Biomedical Sciences (MR/N013700/1). We also acknowledge funding from the UK Department of Health and Social Care via the National Institute for Health Research comprehensive Biomedical Research Center award to Guy's and St. Thomas? National Health Service Foundation Trust in partnership with King's College London and King's College Hospital NHS Foundation Trust. Funding Information: We are grateful to everyone in CSCRM who provided advice and reagents. We thank Alessandra Vigilante and Chi Fung Joseph Ng for support with data analysis, and James Williams, Ruta Meleckyte, and Ana-Maria Cjuba for experimental assistance. This work was supported by grants to F.M.W. from the UK Medical Research Council ( MR/PO18823/1 ) and the Wellcome Trust ( 206439/Z/17/Z ; 098503/Z/12/Z ). A.V. gratefully acknowledges funding from the UK Medical Research Council through the King's College London MRC Doctoral Training Partnership in Biomedical Sciences (MR/N013700/1 ). We also acknowledge funding from the UK Department of Health and Social Care via the National Institute for Health Research comprehensive Biomedical Research Center award to Guy's and St. Thomas’ National Health Service Foundation Trust in partnership with King’s College London and King's College Hospital NHS Foundation Trust. Publisher Copyright: © 2021 The Authors

King's Authors

Abstract

Quantitative analysis of human induced pluripotent stem cell (iPSC) lines from healthy donors is a powerful tool for uncovering the relationship between genetic variants and cellular behavior. We previously identified rare, deleterious non-synonymous single nucleotide variants (nsSNVs) in cell adhesion genes that are associated with outlier iPSC phenotypes in the pluripotent state. Here, we generated micropatterned colonies of iPSCs to test whether nsSNVs influence patterning of radially ordered germ layers. Using a custom-built image analysis pipeline, we quantified the differentiation phenotypes of 13 iPSC lines that harbor nsSNVs in genes related to cell adhesion or germ layer development. All iPSC lines differentiated into the three germ layers; however, there was donor-specific variation in germ layer patterning. We identified one line that presented an outlier phenotype of expanded endodermal differentiation, which was associated with a nsSNV in ITGB1. Our study establishes a platform for investigating the impact of nsSNVs on differentiation.

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