Genetic Variability Overrides the Impact of Parental Cell Type and Determines iPSC Differentiation Potential

Genetic Variability Overrides the Impact of Parental Cell Type and Determines iPSC Differentiation Potential

Reports on the retention of somatic cell memory in induced pluripotent stem cells (iPSCs) have complicated the selection of the optimal cell type for the generation of iPSC biobanks. To address this issue we compared transcriptomic, epigenetic, and differentiation propensities of genetically matched...

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Main Authors: Aija Kyttälä, Roksana Moraghebi, Cristina Valensisi, Johannes Kettunen, Colin Andrus, Kalyan Kumar Pasumarthy, Mahito Nakanishi, Ken Nishimura, Manami Ohtaka, Jere Weltner, Ben Van Handel, Olavi Parkkonen, Juha Sinisalo, Anu Jalanko, R. David Hawkins, Niels-Bjarne Woods, Timo Otonkoski, Ras Trokovic
Format: Article
Language:English
Published: Elsevier 2016-02-01
Series:Stem Cell Reports
Online Access:http://www.sciencedirect.com/science/article/pii/S2213671115003744
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spelling doaj-df19a9ed7811498490d87ed34b5f669f2020-11-24T22:53:45ZengElsevierStem Cell Reports2213-67112016-02-016220021210.1016/j.stemcr.2015.12.009Genetic Variability Overrides the Impact of Parental Cell Type and Determines iPSC Differentiation PotentialAija Kyttälä0Roksana Moraghebi1Cristina Valensisi2Johannes Kettunen3Colin Andrus4Kalyan Kumar Pasumarthy5Mahito Nakanishi6Ken Nishimura7Manami Ohtaka8Jere Weltner9Ben Van Handel10Olavi Parkkonen11Juha Sinisalo12Anu Jalanko13R. David Hawkins14Niels-Bjarne Woods15Timo Otonkoski16Ras Trokovic17Genomics and Biomarkers Unit, National Institute for Health and Welfare (THL), THL Biobank, 00290 Helsinki, FinlandDepartment of Molecular Medicine and Gene Therapy, Lund Stem Cell Center, Lund University, BMC A12, 221 84 Lund, SwedenDivision of Medical Genetics, Departments of Medicine and Genome Sciences, University of Washington, Seattle, WA 98195-7720, USAGenomics and Biomarkers Unit, National Institute for Health and Welfare (THL), THL Biobank, 00290 Helsinki, FinlandDivision of Medical Genetics, Departments of Medicine and Genome Sciences, University of Washington, Seattle, WA 98195-7720, USATurku Centre for Biotechnology, Turku 20520, FinlandBiotechnology Research Institute for Drug Discovery, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki 305-8565, JapanBiotechnology Research Institute for Drug Discovery, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki 305-8565, JapanBiotechnology Research Institute for Drug Discovery, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki 305-8565, JapanResearch Programs Unit, Molecular Neurology and Biomedicum Stem Cell Centre, University of Helsinki, 00290 Helsinki, FinlandNovogenix Laboratories, LLC, Los Angeles, CA 90033, USAHeart and Lung Center, Helsinki University Central Hospital and University of Helsinki, 00029 HUS Helsinki, FinlandHeart and Lung Center, Helsinki University Central Hospital and University of Helsinki, 00029 HUS Helsinki, FinlandGenomics and Biomarkers Unit, National Institute for Health and Welfare (THL), THL Biobank, 00290 Helsinki, FinlandDivision of Medical Genetics, Departments of Medicine and Genome Sciences, University of Washington, Seattle, WA 98195-7720, USADepartment of Molecular Medicine and Gene Therapy, Lund Stem Cell Center, Lund University, BMC A12, 221 84 Lund, SwedenResearch Programs Unit, Molecular Neurology and Biomedicum Stem Cell Centre, University of Helsinki, 00290 Helsinki, FinlandResearch Programs Unit, Molecular Neurology and Biomedicum Stem Cell Centre, University of Helsinki, 00290 Helsinki, FinlandReports on the retention of somatic cell memory in induced pluripotent stem cells (iPSCs) have complicated the selection of the optimal cell type for the generation of iPSC biobanks. To address this issue we compared transcriptomic, epigenetic, and differentiation propensities of genetically matched human iPSCs derived from fibroblasts and blood, two tissues of the most practical relevance for biobanking. Our results show that iPSC lines derived from the same donor are highly similar to each other. However, genetic variation imparts a donor-specific expression and methylation profile in reprogrammed cells that leads to variable functional capacities of iPSC lines. Our results suggest that integration-free, bona fide iPSC lines from fibroblasts and blood can be combined in repositories to form biobanks. Due to the impact of genetic variation on iPSC differentiation, biobanks should contain cells from large numbers of donors.http://www.sciencedirect.com/science/article/pii/S2213671115003744
collection DOAJ
language English
format Article
sources DOAJ
author Aija Kyttälä
Roksana Moraghebi
Cristina Valensisi
Johannes Kettunen
Colin Andrus
Kalyan Kumar Pasumarthy
Mahito Nakanishi
Ken Nishimura
Manami Ohtaka
Jere Weltner
Ben Van Handel
Olavi Parkkonen
Juha Sinisalo
Anu Jalanko
R. David Hawkins
Niels-Bjarne Woods
Timo Otonkoski
Ras Trokovic
spellingShingle Aija Kyttälä
Roksana Moraghebi
Cristina Valensisi
Johannes Kettunen
Colin Andrus
Kalyan Kumar Pasumarthy
Mahito Nakanishi
Ken Nishimura
Manami Ohtaka
Jere Weltner
Ben Van Handel
Olavi Parkkonen
Juha Sinisalo
Anu Jalanko
R. David Hawkins
Niels-Bjarne Woods
Timo Otonkoski
Ras Trokovic
Genetic Variability Overrides the Impact of Parental Cell Type and Determines iPSC Differentiation Potential
Stem Cell Reports
author_facet Aija Kyttälä
Roksana Moraghebi
Cristina Valensisi
Johannes Kettunen
Colin Andrus
Kalyan Kumar Pasumarthy
Mahito Nakanishi
Ken Nishimura
Manami Ohtaka
Jere Weltner
Ben Van Handel
Olavi Parkkonen
Juha Sinisalo
Anu Jalanko
R. David Hawkins
Niels-Bjarne Woods
Timo Otonkoski
Ras Trokovic
author_sort Aija Kyttälä
title Genetic Variability Overrides the Impact of Parental Cell Type and Determines iPSC Differentiation Potential
title_short Genetic Variability Overrides the Impact of Parental Cell Type and Determines iPSC Differentiation Potential
title_full Genetic Variability Overrides the Impact of Parental Cell Type and Determines iPSC Differentiation Potential
title_fullStr Genetic Variability Overrides the Impact of Parental Cell Type and Determines iPSC Differentiation Potential
title_full_unstemmed Genetic Variability Overrides the Impact of Parental Cell Type and Determines iPSC Differentiation Potential
title_sort genetic variability overrides the impact of parental cell type and determines ipsc differentiation potential
publisher Elsevier
series Stem Cell Reports
issn 2213-6711
publishDate 2016-02-01
description Reports on the retention of somatic cell memory in induced pluripotent stem cells (iPSCs) have complicated the selection of the optimal cell type for the generation of iPSC biobanks. To address this issue we compared transcriptomic, epigenetic, and differentiation propensities of genetically matched human iPSCs derived from fibroblasts and blood, two tissues of the most practical relevance for biobanking. Our results show that iPSC lines derived from the same donor are highly similar to each other. However, genetic variation imparts a donor-specific expression and methylation profile in reprogrammed cells that leads to variable functional capacities of iPSC lines. Our results suggest that integration-free, bona fide iPSC lines from fibroblasts and blood can be combined in repositories to form biobanks. Due to the impact of genetic variation on iPSC differentiation, biobanks should contain cells from large numbers of donors.
url http://www.sciencedirect.com/science/article/pii/S2213671115003744
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