Random Mutagenesis, Clonal Events, and Embryonic or Somatic Origin Determine the mtDNA Variant Type and Load in Human Pluripotent Stem Cells.

Fiche publication

Date publication

juin 2018

Journal

Stem cell reports

Auteurs

Membres identifiés du Cancéropôle Est :
Pr VIVILLE Stéphane

Tous les auteurs :
Zambelli F, Mertens J, Dziedzicka D, Sterckx J, Markouli C, Keller A, Tropel P, Jung L, Viville S, Van de Velde H, Geens M, Seneca S, Sermon K, Spits C

Lien Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/29910126

Résumé

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.