Journal
STEM CELL REPORTS
Volume 11, Issue 1, Pages 102-114Publisher
CELL PRESS
DOI: 10.1016/j.stemcr.2018.05.007
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Funding
- Wetenschappelijke Fonds Willy Gepts (UZ Brussel)
- FWO-Vlaanderen [1506616N]
- Vrije Universiteit Brussel
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In this study, we deep-sequenced the mtDNA of human embryonic and induced pluripotent stem cells (hESCs and hiPSCs) and their source cells and found that the majority of variants pre-existed in the cells used to establish the lines. Early-passage hESCs carried few and low-load heteroplasmic variants, similar to those identified in oocytes and inner cell masses. The number and heteroplasmic loads of these variants increased with prolonged cell culture. The study of 120 individual cells of early- and late-passage hESCs revealed a significant diversity in mtDNA heteroplasmic variants at the single-cell level and that the variants that increase during time in culture are always passenger to the appearance of chromosomal abnormalities. We found that early-passage hiPSCs carry much higher loads of mtDNA variants than hESCs, which single-fibroblast sequencing proved pre-existed in the source cells. Finally, we show that these variants are stably transmitted during short-term differentiation.
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