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

Research output: Contribution to journalArticle

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.

Details

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
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cell and Molecular Biology
Original languageEnglish
Pages (from-to)200-212
JournalStem Cell Reports
Volume6
Issue number2
Early online date2016 Jan 12
Publication statusPublished - 2016
Publication categoryResearch
Peer-reviewedYes

Related research output

Moraghebi, R., 2017, Lund: Lund University: Faculty of Medicine. 88 p.

Research output: ThesisDoctoral Thesis (compilation)

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