Feeder-free culture of human pluripotent stem cells drives MDM4-mediated gain of chromosome 1q.

Autor:	Stavish D; Centre for Stem Cell Biology, School of Biosciences, The University of Sheffield, Sheffield, UK; Neuroscience Institute, The University of Sheffield, Sheffield, UK; INSIGNEO Institute, The University of Sheffield, Sheffield, UK., Price CJ; Centre for Stem Cell Biology, School of Biosciences, The University of Sheffield, Sheffield, UK; Neuroscience Institute, The University of Sheffield, Sheffield, UK; INSIGNEO Institute, The University of Sheffield, Sheffield, UK., Gelezauskaite G; Centre for Stem Cell Biology, School of Biosciences, The University of Sheffield, Sheffield, UK; Neuroscience Institute, The University of Sheffield, Sheffield, UK; INSIGNEO Institute, The University of Sheffield, Sheffield, UK., Alsehli H; Centre for Stem Cell Biology, School of Biosciences, The University of Sheffield, Sheffield, UK; Neuroscience Institute, The University of Sheffield, Sheffield, UK; INSIGNEO Institute, The University of Sheffield, Sheffield, UK., Leonhard KA; WiCell Research Institute, Madison, WI, USA., Taapken SM; WiCell Research Institute, Madison, WI, USA., McIntire EM; WiCell Research Institute, Madison, WI, USA; Department of Human Genetics, University of Chicago, Chicago, IL, USA., Laing O; Centre for Stem Cell Biology, School of Biosciences, The University of Sheffield, Sheffield, UK; Neuroscience Institute, The University of Sheffield, Sheffield, UK; INSIGNEO Institute, The University of Sheffield, Sheffield, UK., James BM; Centre for Stem Cell Biology, School of Biosciences, The University of Sheffield, Sheffield, UK; Neuroscience Institute, The University of Sheffield, Sheffield, UK; INSIGNEO Institute, The University of Sheffield, Sheffield, UK., Riley JJ; Centre for Stem Cell Biology, School of Biosciences, The University of Sheffield, Sheffield, UK., Zerbib J; Department of Human Molecular Genetics and Biochemistry, Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel., Baker D; Sheffield Diagnostic Genetic Services, Sheffield Children's Hospital, Sheffield, UK., Harding AL; School of Clinical Dentistry, University of Sheffield, Sheffield, UK., Jestice LH; Centre for Stem Cell Biology, School of Biosciences, The University of Sheffield, Sheffield, UK; Neuroscience Institute, The University of Sheffield, Sheffield, UK; INSIGNEO Institute, The University of Sheffield, Sheffield, UK., Eleveld TF; Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands., Gillis AJM; Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands., Hillenius S; Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands., Looijenga LHJ; Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands., Gokhale PJ; Centre for Stem Cell Biology, School of Biosciences, The University of Sheffield, Sheffield, UK; Neuroscience Institute, The University of Sheffield, Sheffield, UK; INSIGNEO Institute, The University of Sheffield, Sheffield, UK., Ben-David U; Department of Human Molecular Genetics and Biochemistry, Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel., Ludwig TE; WiCell Research Institute, Madison, WI, USA; Office of the Vice Chancellor for Research and Graduate Education, University of Wisconsin-Madison, Madison, WI, USA., Barbaric I; Centre for Stem Cell Biology, School of Biosciences, The University of Sheffield, Sheffield, UK; Neuroscience Institute, The University of Sheffield, Sheffield, UK; INSIGNEO Institute, The University of Sheffield, Sheffield, UK. Electronic address: i.barbaric@sheffield.ac.uk.
Jazyk:	angličtina
Zdroj:	Stem cell reports [Stem Cell Reports] 2024 Aug 13; Vol. 19 (8), pp. 1217-1232. Date of Electronic Publication: 2024 Jul 03.
DOI:	10.1016/j.stemcr.2024.06.003
Abstrakt:	Culture-acquired variants in human pluripotent stem cells (hPSCs) hinder their applications in research and clinic. However, the mechanisms that underpin selection of variants remain unclear. Here, through analysis of comprehensive karyotyping datasets from over 23,000 hPSC cultures of more than 1,500 lines, we explored how culture conditions shape variant selection. Strikingly, we identified an association of chromosome 1q gains with feeder-free cultures and noted a rise in its prevalence in recent years, coinciding with increased usage of feeder-free regimens. Competition experiments of multiple isogenic lines with and without a chromosome 1q gain confirmed that 1q variants have an advantage in feeder-free (E8/vitronectin), but not feeder-based, culture. Mechanistically, we show that overexpression of MDM4, located on chromosome 1q, drives variants' advantage in E8/vitronectin by alleviating genome damage-induced apoptosis, which is lower in feeder-based conditions. Our study explains condition-dependent patterns of hPSC aberrations and offers insights into the mechanisms of variant selection. Competing Interests: Declaration of interests T.E.L. is a co-inventor and receives a share of royalties on various hPSC media- and culture-related patents currently owned and licensed by the Wisconsin Alumni Research Foundation (WARF). I.B. is a member of the scientific advisory board of WiCell. U.B.-D. received consulting fees from Accent Therapeutics. (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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