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

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

doi:10.1016/j.stemcr.2015.12.009

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

Stem Cell Reports. 2016 Feb 9;6(2):200-12. doi: 10.1016/j.stemcr.2015.12.009. Epub 2016 Jan 14.

Authors

Aija Kyttälä¹, Roksana Moraghebi², Cristina Valensisi³, Johannes Kettunen⁴, Colin Andrus⁵, Kalyan Kumar Pasumarthy⁶, Mahito Nakanishi⁷, Ken Nishimura⁸, Manami Ohtaka⁷, Jere Weltner⁹, Ben Van Handel¹⁰, Olavi Parkkonen¹¹, Juha Sinisalo¹¹, Anu Jalanko¹, R David Hawkins³, Niels-Bjarne Woods², Timo Otonkoski¹², Ras Trokovic¹³

Affiliations

¹ Genomics and Biomarkers Unit, National Institute for Health and Welfare (THL), THL Biobank, 00290 Helsinki, Finland.
² Department of Molecular Medicine and Gene Therapy, Lund Stem Cell Center, Lund University, BMC A12, 221 84 Lund, Sweden.
³ 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.
⁴ 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.
⁵ Division of Medical Genetics, Departments of Medicine and Genome Sciences, University of Washington, Seattle, WA 98195-7720, USA.
⁶ Turku Centre for Biotechnology, Turku 20520, Finland.
⁷ Biotechnology Research Institute for Drug Discovery, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki 305-8565, Japan.
⁸ 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.
⁹ Research Programs Unit, Molecular Neurology and Biomedicum Stem Cell Centre, University of Helsinki, 00290 Helsinki, Finland.
¹⁰ Novogenix Laboratories, LLC, Los Angeles, CA 90033, USA.
¹¹ Heart and Lung Center, Helsinki University Central Hospital and University of Helsinki, 00029 HUS Helsinki, Finland.
¹² 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.
¹³ Research Programs Unit, Molecular Neurology and Biomedicum Stem Cell Centre, University of Helsinki, 00290 Helsinki, Finland. Electronic address: ras.trokovic@helsinki.fi.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Biological Specimen Banks
Cell Differentiation / genetics*
DNA Methylation / genetics
Epigenesis, Genetic
Erythroid Cells / cytology
Female
Fibroblasts / metabolism
Genetic Variation*
Hematopoiesis / genetics
Humans
Induced Pluripotent Stem Cells / cytology*
Male
Tissue Donors
Transcription, Genetic