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Cellular heterogeneity in the level of mtDNA heteroplasmy in mouse embryonic stem cells

Jitesh Neupane (UGent) , Sabitri Ghimire (UGent) , Mado Vandewoestyne (UGent) , Yuechao Lu (UGent) , Jan Gerris (UGent) , Rudy Van Coster (UGent) , Tom Deroo (UGent) , Dieter Deforce (UGent) , Stijn Vansteelandt (UGent) , Petra De Sutter (UGent) , et al.
(2015) CELL REPORTS. 13(7). p.1304-1309
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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.
Keywords
TRANSMISSION, MICE, REPLICATION, PATIENT, RAPID SEGREGATION, POLAR BODIES, DISEASES, MITOCHONDRIAL-DNA, TRNALEU(UUR) POINT MUTATION, PREIMPLANTATION GENETIC DIAGNOSIS

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Chicago
Neupane, Jitesh, Sabitri Ghimire, Mado Vandewoestyne, Yuechao Lu, Jan Gerris, Rudy Van Coster, Tom Deroo, et al. 2015. “Cellular Heterogeneity in the Level of mtDNA Heteroplasmy in Mouse Embryonic Stem Cells.” Cell Reports 13 (7): 1304–1309.
APA
Neupane, J., Ghimire, S., Vandewoestyne, M., Lu, Y., Gerris, J., Van Coster, R., Deroo, T., et al. (2015). Cellular heterogeneity in the level of mtDNA heteroplasmy in mouse embryonic stem cells. CELL REPORTS, 13(7), 1304–1309.
Vancouver
1.
Neupane J, Ghimire S, Vandewoestyne M, Lu Y, Gerris J, Van Coster R, et al. Cellular heterogeneity in the level of mtDNA heteroplasmy in mouse embryonic stem cells. CELL REPORTS. 2015;13(7):1304–9.
MLA
Neupane, Jitesh, Sabitri Ghimire, Mado Vandewoestyne, et al. “Cellular Heterogeneity in the Level of mtDNA Heteroplasmy in Mouse Embryonic Stem Cells.” CELL REPORTS 13.7 (2015): 1304–1309. Print.
@article{7017697,
  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.},
  author       = {Neupane, Jitesh and Ghimire, Sabitri and Vandewoestyne, Mado and Lu, Yuechao and Gerris, Jan and Van Coster, Rudy and Deroo, Tom and Deforce, Dieter and Vansteelandt, Stijn and De Sutter, Petra and Heindryckx, Bj{\"o}rn},
  issn         = {2211-1247},
  journal      = {CELL REPORTS},
  keyword      = {TRANSMISSION,MICE,REPLICATION,PATIENT,RAPID SEGREGATION,POLAR BODIES,DISEASES,MITOCHONDRIAL-DNA,TRNALEU(UUR) POINT MUTATION,PREIMPLANTATION GENETIC DIAGNOSIS},
  language     = {eng},
  number       = {7},
  pages        = {1304--1309},
  title        = {Cellular heterogeneity in the level of mtDNA heteroplasmy in mouse embryonic stem cells},
  url          = {http://dx.doi.org/10.1016/j.celrep.2015.10.019},
  volume       = {13},
  year         = {2015},
}

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