Evidence map›Paper›PMID 21994000›Full record

ArticleStem cell reviews and reports2013

The effects of nuclear reprogramming on mitochondrial DNA replication.

Richard D W Kelly, Huseyin Sumer, Matthew McKenzie, Joao Facucho-Oliveira, Ian A Trounce, Paul J Verma, Justin C St John

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Article in Stem cell reviews and reports, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

28 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. Article
  5. The role of mtDNA in oocyte quality and embryo development.Molecular reproduction and development · 2023
    Review
  6. Review
  7. Article
  8. Article
  9. Review
  10. Review
  11. Article
  12. Article
  13. Article
  14. Article
  15. Review
  16. Review
  17. Article
  18. Article
  19. Metabolic restructuring and cell fate conversion.Cellular and molecular life sciences : CMLS · 2015
    Review
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors.

Richard D W KellyCentre for Reproduction and Development, Monash Institute of Medical Research, Monash University, 27-31 Wright Street, Clayton, Victoria, 3168, Australia.
Huseyin Sumer
Matthew McKenzie
Joao Facucho-Oliveira
Ian A Trounce
Paul J Verma
Justin C St John

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Undifferentiated mouse embryonic stem cells (ESCs) possess low numbers of mitochondrial DNA (mtDNA), which encodes key subunits associated with the generation of ATP through oxidative phosphorylation (OXPHOS). As ESCs differentiate, mtDNA copy number is regulated by the nuclear-encoded mtDNA replication factors, which initiate a major replication event on Day 6 of differentiation. Here, we examined mtDNA replication events in somatic cells reprogrammed to pluripotency, namely somatic cell-ES (SC-ES), somatic cell nuclear transfer ES (NT-ES) and induced pluripotent stem (iPS) cells, all at low-passage. MtDNA copy number in undifferentiated iPS cells was similar to ESCs whilst SC-ES and NT-ES cells had significantly increased levels, which correlated positively and negatively with Nanog and Sox2 expression, respectively. During pluripotency and differentiation, the expression of the mtDNA-specific replication factors, PolgA and Peo1, were differentially expressed in iPS and SC-ES cells when compared to ESCs. Throughout differentiation, reprogrammed somatic cells were unable to accumulate mtDNA copy number, characteristic of ESCs, especially on Day 6. In addition, iPS and SC-ES cells were also unable to regulate ATP content in a manner similar to differentiating ESCs prior to Day 14. The treatment of reprogrammed somatic cells with an inhibitor of de novo DNA methylation, 5-Azacytidine, prior to differentiation enabled iPS cells, but not SC-ES and NT-ES cells, to accumulate mtDNA copies per cell in a manner similar to ESCs. These data demonstrate that the reprogramming process disrupts the regulation of mtDNA replication during pluripotency but this can be re-established through the use of epigenetic modifiers.

Indexed as

Cellular ReprogrammingDNA Copy Number VariationsDNA ReplicationAnimalsAzacitidineCell DifferentiationCell NucleusCells, CulturedDNA-Directed DNA PolymeraseDNA HelicasesDNA, MitochondrialDNA Polymerase gammaEmbryonic Stem CellsEnzyme InhibitorsHomeodomain ProteinsInduced Pluripotent Stem CellsAzacitidineDNA-Directed DNA PolymeraseDNA HelicasesDNA, MitochondrialDNA Polymerase gammaEnzyme InhibitorsHomeodomain ProteinsMitochondrial ProteinsNanog Homeobox ProteinNanog protein, mouseOctamer Transcription Factor-3Polg protein, mousePou5f1 protein, mouserhodamine 6GRhodaminesSox2 protein, mouseSOXB1 Transcription FactorsTwnk protein, mouse

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.