Show simple item record

dc.contributor.authorWei, Wei
dc.contributor.authorGaffney, Daniel J
dc.contributor.authorChinnery, Patrick F
dc.date.accessioned2021-10-05T00:26:36Z
dc.date.available2021-10-05T00:26:36Z
dc.date.issued2021-09-02
dc.identifier.issn2041-1723
dc.identifier.other34475388
dc.identifier.otherPMC8413449
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/328995
dc.description.abstractIndividual induced pluripotent stem cells (iPSCs) show considerable phenotypic heterogeneity, but the reasons for this are not fully understood. Comprehensively analysing the mitochondrial genome (mtDNA) in 146 iPSC and fibroblast lines from 151 donors, we show that most age-related fibroblast mtDNA mutations are lost during reprogramming. However, iPSC-specific mutations are seen in 76.6% (108/141) of iPSC lines at a mutation rate of 8.62 × 10<sup>-5</sup>/base pair. The mutations observed in iPSC lines affect a higher proportion of mtDNA molecules, favouring non-synonymous protein-coding and tRNA variants, including known disease-causing mutations. Analysing 11,538 single cells shows stable heteroplasmy in sub-clones derived from the original donor during differentiation, with mtDNA variants influencing the expression of key genes involved in mitochondrial metabolism and epidermal cell differentiation. Thus, the dynamic mtDNA landscape contributes to the heterogeneity of human iPSCs and should be considered when using reprogrammed cells experimentally or as a therapy.
dc.languageeng
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.sourceessn: 2041-1723
dc.sourcenlmid: 101528555
dc.subjectFibroblasts
dc.subjectHumans
dc.subjectDNA, Mitochondrial
dc.subjectGene Expression
dc.subjectMutation
dc.subjectAdult
dc.subjectAged
dc.subjectMiddle Aged
dc.subjectFemale
dc.subjectMale
dc.subjectGenome, Mitochondrial
dc.subjectYoung Adult
dc.subjectInduced Pluripotent Stem Cells
dc.subjectCellular Reprogramming
dc.subjectCellular Senescence
dc.subjectHeteroplasmy
dc.titleCell reprogramming shapes the mitochondrial DNA landscape.
dc.typeArticle
dc.date.updated2021-10-05T00:26:36Z
prism.issueIdentifier1
prism.publicationNameNature communications
prism.volume12
dc.identifier.doi10.17863/CAM.76439
rioxxterms.versionofrecord10.1038/s41467-021-25482-x
rioxxterms.versionVoR
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0/
dc.contributor.orcidGaffney, Daniel J [0000-0002-1529-1862]
dc.contributor.orcidChinnery, Patrick F [0000-0002-7065-6617]
pubs.funder-project-idWellcome Trust (212219/Z/18/Z)
pubs.funder-project-idMedical Research Council (MC_UU_00015/9)
pubs.funder-project-idAlzheimer's Society (022)
pubs.funder-project-idLeverhulme Trust (RPG-2018-408)
pubs.funder-project-idRCUK | Medical Research Council (MC_UU_00015/9)


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record

Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International