title: Cellular Heterogeneity in the Level of mtDNA Heteroplasmy in Mouse Embryonic Stem Cells.
abstract: Variation in the level of mtDNA heteroplasmy in adult tissues is commonly seen in patients with a mixture of wild-type and mutant mtDNA. A mixture of different mtDNA variants may influence such variation and cause mtDNA segregation bias. We analyzed cellular heterogeneity in embryonic stem cells (ESCs) derived from a polymorphic mouse model containing NZB and BALB mtDNA genotypes. In ESCs, inter-colony heterogeneity varied up to 61%, whereas intra-colony heterogeneity varied up to 100%. Three out of five cell lines displayed nearly homoplasmic BALB and NZB mtDNA haplotypes in differentiated single cells. The proportion of NZB mtDNA genotype increased with progressive passaging (0.39%; p = 0.002). These results demonstrate the bimodal segregation of mtDNA haplotypes, indicating the occurrence of tissues with variable levels of heteroplasmies in individuals with mtDNA mutations. Furthermore, proliferation of one mtDNA genotype over another may pose the risk of accumulating mutant mtDNAs during subsequent cell divisions.
authors.affiliation: Ghent Fertility and Stem Cell Team (G-FaST), Department for Reproductive Medicine, Ghent University Hospital, De Pintelaan 185, 9000 Ghent, Belgium. Electronic address: jitesh.neupane@ugent.be.
authors.forename: Jitesh
authors.initials: J
authors.lastname: Neupane
authors.affiliation: Ghent Fertility and Stem Cell Team (G-FaST), Department for Reproductive Medicine, Ghent University Hospital, De Pintelaan 185, 9000 Ghent, Belgium.
authors.forename: Sabitri
authors.initials: S
authors.lastname: Ghimire
authors.affiliation: Laboratory of Pharmaceutical Biotechnology, Ghent University, Ottergemsesteenweg 460, 9000 Ghent, Belgium.
authors.forename: Mado
authors.initials: M
authors.lastname: Vandewoestyne
authors.affiliation: Ghent Fertility and Stem Cell Team (G-FaST), Department for Reproductive Medicine, Ghent University Hospital, De Pintelaan 185, 9000 Ghent, Belgium.
authors.forename: Yuechao
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Ghent Fertility and Stem Cell Team (G-FaST), Department for Reproductive Medicine, Ghent University Hospital, De Pintelaan 185, 9000 Ghent, Belgium.
authors.forename: Jan
authors.initials: J
authors.lastname: Gerris
authors.affiliation: Department of Paediatric Neurology and Metabolism, Ghent University Hospital, De Pintelaan 185, 9000 Ghent, Belgium.
authors.forename: Rudy
authors.initials: R
authors.lastname: Van Coster
authors.affiliation: Ghent Fertility and Stem Cell Team (G-FaST), Department for Reproductive Medicine, Ghent University Hospital, De Pintelaan 185, 9000 Ghent, Belgium.
authors.forename: Tom
authors.initials: T
authors.lastname: Deroo
authors.affiliation: Laboratory of Pharmaceutical Biotechnology, Ghent University, Ottergemsesteenweg 460, 9000 Ghent, Belgium.
authors.forename: Dieter
authors.initials: D
authors.lastname: Deforce
authors.affiliation: Department of Applied Mathematics, Computer Science and Statistics, Ghent University, Krijgslaan 281, S9 9000 Gent, Belgium.
authors.forename: Stijn
authors.initials: S
authors.lastname: Vansteelandt
authors.affiliation: Ghent Fertility and Stem Cell Team (G-FaST), Department for Reproductive Medicine, Ghent University Hospital, De Pintelaan 185, 9000 Ghent, Belgium.
authors.forename: Petra
authors.initials: P
authors.lastname: De Sutter
authors.affiliation: Ghent Fertility and Stem Cell Team (G-FaST), Department for Reproductive Medicine, Ghent University Hospital, De Pintelaan 185, 9000 Ghent, Belgium. Electronic address: bjorn.heindryckx@ugent.be.
authors.forename: Björn
authors.initials: B
authors.lastname: Heindryckx
mesh_terms: D000818:Animals; D002455:Cell Division; D002478:Cells, Cultured; D004272:DNA, Mitochondrial / Q000235:genetics*; D018740:Genetic Heterogeneity; D006239:Haplotypes; D051379:Mice; D000066450:Mouse Embryonic Stem Cells / Q000502:physiology*
chemical_list: D004272:DNA, Mitochondrial