title: Genetic Variability Overrides the Impact of Parental Cell Type and Determines iPSC Differentiation Potential.
abstract: 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.
authors.affiliation: Genomics and Biomarkers Unit, National Institute for Health and Welfare (THL), THL Biobank, 00290 Helsinki, Finland.
authors.forename: Aija
authors.initials: A
authors.lastname: Kyttälä
authors.affiliation: Department of Molecular Medicine and Gene Therapy, Lund Stem Cell Center, Lund University, BMC A12, 221 84 Lund, Sweden.
authors.forename: Roksana
authors.initials: R
authors.lastname: Moraghebi
authors.affiliation: Division of Medical Genetics, Departments of Medicine and Genome Sciences, University of Washington, Seattle, WA 98195-7720, USA; Turku Centre for Biotechnology, Turku 20520, Finland.
authors.forename: Cristina
authors.initials: C
authors.lastname: Valensisi
authors.affiliation: Genomics and Biomarkers Unit, National Institute for Health and Welfare (THL), THL Biobank, 00290 Helsinki, Finland; Computational Medicine, Institute of Health Sciences, University of Oulu, Oulu 90014, Finland; NMR Metabolomics Laboratory, School of Pharmacy, University of Eastern Finland, Kuopio 70210, Finland; Biocenter Oulu, University of Oulu, 90014 Oulu, Finland.
authors.forename: Johannes
authors.initials: J
authors.lastname: Kettunen
authors.affiliation: Division of Medical Genetics, Departments of Medicine and Genome Sciences, University of Washington, Seattle, WA 98195-7720, USA.
authors.forename: Colin
authors.initials: C
authors.lastname: Andrus
authors.affiliation: Turku Centre for Biotechnology, Turku 20520, Finland.
authors.forename: Kalyan Kumar
authors.initials: KK
authors.lastname: Pasumarthy
authors.affiliation: Biotechnology Research Institute for Drug Discovery, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki 305-8565, Japan.
authors.forename: Mahito
authors.initials: M
authors.lastname: Nakanishi
authors.affiliation: Biotechnology Research Institute for Drug Discovery, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki 305-8565, Japan; Laboratory of Gene Regulation, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Nishimura
authors.affiliation: Biotechnology Research Institute for Drug Discovery, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki 305-8565, Japan.
authors.forename: Manami
authors.initials: M
authors.lastname: Ohtaka
authors.affiliation: Research Programs Unit, Molecular Neurology and Biomedicum Stem Cell Centre, University of Helsinki, 00290 Helsinki, Finland.
authors.forename: Jere
authors.initials: J
authors.lastname: Weltner
authors.affiliation: Novogenix Laboratories, LLC, Los Angeles, CA 90033, USA.
authors.forename: Ben
authors.initials: B
authors.lastname: Van Handel
authors.affiliation: Heart and Lung Center, Helsinki University Central Hospital and University of Helsinki, 00029 HUS Helsinki, Finland.
authors.forename: Olavi
authors.initials: O
authors.lastname: Parkkonen
authors.affiliation: Heart and Lung Center, Helsinki University Central Hospital and University of Helsinki, 00029 HUS Helsinki, Finland.
authors.forename: Juha
authors.initials: J
authors.lastname: Sinisalo
authors.affiliation: Genomics and Biomarkers Unit, National Institute for Health and Welfare (THL), THL Biobank, 00290 Helsinki, Finland.
authors.forename: Anu
authors.initials: A
authors.lastname: Jalanko
authors.affiliation: Division of Medical Genetics, Departments of Medicine and Genome Sciences, University of Washington, Seattle, WA 98195-7720, USA; Turku Centre for Biotechnology, Turku 20520, Finland.
authors.forename: R David
authors.initials: RD
authors.lastname: Hawkins
authors.affiliation: Department of Molecular Medicine and Gene Therapy, Lund Stem Cell Center, Lund University, BMC A12, 221 84 Lund, Sweden.
authors.forename: Niels-Bjarne
authors.initials: NB
authors.lastname: Woods
authors.affiliation: Research Programs Unit, Molecular Neurology and Biomedicum Stem Cell Centre, University of Helsinki, 00290 Helsinki, Finland; Children's Hospital, University of Helsinki and Helsinki University Central Hospital, 00029 HUS Helsinki, Finland. Electronic address: timo.otonkoski@helsinki.fi.
authors.forename: Timo
authors.initials: T
authors.lastname: Otonkoski
authors.affiliation: Research Programs Unit, Molecular Neurology and Biomedicum Stem Cell Centre, University of Helsinki, 00290 Helsinki, Finland. Electronic address: ras.trokovic@helsinki.fi.
authors.forename: Ras
authors.initials: R
authors.lastname: Trokovic
mesh_terms: D018070:Biological Specimen Banks; D002454:Cell Differentiation / Q000235:genetics*; D019175:DNA Methylation / Q000235:genetics; D044127:Epigenesis, Genetic; D041905:Erythroid Cells / Q000166:cytology; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D014644:Genetic Variation; D006410:Hematopoiesis / Q000235:genetics; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology*; D008297:Male; D014019:Tissue Donors; D014158:Transcription, Genetic