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

Stem Cell Reports (Feb 2016)

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

Affiliations

Aija Kyttälä: Genomics and Biomarkers Unit, National Institute for Health and Welfare (THL), THL Biobank, 00290 Helsinki, Finland
Roksana Moraghebi: Department of Molecular Medicine and Gene Therapy, Lund Stem Cell Center, Lund University, BMC A12, 221 84 Lund, Sweden
Cristina Valensisi: Division of Medical Genetics, Departments of Medicine and Genome Sciences, University of Washington, Seattle, WA 98195-7720, USA
Johannes Kettunen: Genomics and Biomarkers Unit, National Institute for Health and Welfare (THL), THL Biobank, 00290 Helsinki, Finland
Colin Andrus: Division of Medical Genetics, Departments of Medicine and Genome Sciences, University of Washington, Seattle, WA 98195-7720, USA
Kalyan Kumar Pasumarthy: Turku Centre for Biotechnology, Turku 20520, Finland
Mahito Nakanishi: Biotechnology Research Institute for Drug Discovery, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki 305-8565, Japan
Ken Nishimura: Biotechnology Research Institute for Drug Discovery, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki 305-8565, Japan
Manami Ohtaka: Biotechnology Research Institute for Drug Discovery, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki 305-8565, Japan
Jere Weltner: Research Programs Unit, Molecular Neurology and Biomedicum Stem Cell Centre, University of Helsinki, 00290 Helsinki, Finland
Ben Van Handel: Novogenix Laboratories, LLC, Los Angeles, CA 90033, USA
Olavi Parkkonen: Heart and Lung Center, Helsinki University Central Hospital and University of Helsinki, 00029 HUS Helsinki, Finland
Juha Sinisalo: Heart and Lung Center, Helsinki University Central Hospital and University of Helsinki, 00029 HUS Helsinki, Finland
Anu Jalanko: Genomics and Biomarkers Unit, National Institute for Health and Welfare (THL), THL Biobank, 00290 Helsinki, Finland
R. David Hawkins: Division of Medical Genetics, Departments of Medicine and Genome Sciences, University of Washington, Seattle, WA 98195-7720, USA
Niels-Bjarne Woods: Department of Molecular Medicine and Gene Therapy, Lund Stem Cell Center, Lund University, BMC A12, 221 84 Lund, Sweden
Timo Otonkoski: Research Programs Unit, Molecular Neurology and Biomedicum Stem Cell Centre, University of Helsinki, 00290 Helsinki, Finland
Ras Trokovic: Research Programs Unit, Molecular Neurology and Biomedicum Stem Cell Centre, University of Helsinki, 00290 Helsinki, Finland

DOI: https://doi.org/10.1016/j.stemcr.2015.12.009
Journal volume & issue: Vol. 6, no. 2
pp. 200 – 212

Abstract

Read online

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.

Published in Stem Cell Reports

ISSN: 2213-6711 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Medicine (General); Science: Biology (General)
Website: http://www.cell.com/stem-cell-reports/home

About the journal