Back to Search
Start Over
Cellular Heterogeneity in the Level of mtDNA Heteroplasmy in Mouse Embryonic Stem Cells
- Source :
- CELL REPORTS, Cell Reports, Vol 13, Iss 7, Pp 1304-1309 (2015)
- Publisher :
- The Authors. Published by Elsevier Inc.
-
Abstract
- SummaryVariation 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.
- Subjects :
- Mitochondrial DNA
Cell division
TRANSMISSION
MITOCHONDRIAL-DNA
PREIMPLANTATION GENETIC DIAGNOSIS
TRNALEU(UUR) POINT MUTATION
Mutant
Biology
DNA, Mitochondrial
PATIENT
General Biochemistry, Genetics and Molecular Biology
Genetic Heterogeneity
Mice
POLAR BODIES
Genotype
Medicine and Health Sciences
Animals
RAPID SEGREGATION
lcsh:QH301-705.5
Cells, Cultured
Genetics
Genetic heterogeneity
Haplotype
Mouse Embryonic Stem Cells
Embryonic stem cell
Molecular biology
Heteroplasmy
MICE
lcsh:Biology (General)
Haplotypes
DISEASES
REPLICATION
Cell Division
Subjects
Details
- Language :
- English
- ISSN :
- 22111247
- Issue :
- 7
- Database :
- OpenAIRE
- Journal :
- Cell Reports
- Accession number :
- edsair.doi.dedup.....40c564ad43d6cc32e801d83e76845adb
- Full Text :
- https://doi.org/10.1016/j.celrep.2015.10.019