Evidence map›Paper›PMID 29358089›Full record

ArticleStem cell reports2018

BAK/BAX-Mediated Apoptosis Is a Myc-Induced Roadblock to Reprogramming.

Esther J Y Kim, Minna-Liisa Anko, Christoffer Flensberg, Ian J Majewski, Fan-Suo Geng, Jaber Firas, David C S Huang, Mark F van Delft, Joan K Heath

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Stem cell reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing 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

12 citing papers in PubMed.

  1. Review
  2. Review
  3. Article
  4. Article
  5. Realgar (AsAging · 2022
    Article
  6. Article
  7. Review
  8. Review
  9. Article
  10. Review
  11. Review
  12. Cellular trajectories and molecular mechanisms of iPSC reprogramming.Current opinion in genetics & development · 2018
    Review
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

9 authors.

Esther J Y KimThe Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, VIC 3052, Australia.
Minna-Liisa AnkoDepartment of Anatomy and Developmental Biology, Biomedicine Discovery Institute, Development and Stem Cells Program, Monash University, Clayton, VIC 3800, Australia.
Christoffer FlensbergThe Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, VIC 3052, Australia.
Ian J MajewskiThe Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, VIC 3052, Australia.
Fan-Suo GengThe Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, VIC 3052, Australia.
Jaber FirasDepartment of Anatomy and Developmental Biology, Biomedicine Discovery Institute, Development and Stem Cells Program, Monash University, Clayton, VIC 3800, Australia.
David C S HuangThe Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, VIC 3052, Australia.
Mark F van DelftThe Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, VIC 3052, Australia. Electronic address: vandelft@wehi.edu.au.
Joan K HeathThe Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, VIC 3052, Australia. Electronic address: joan.heath@wehi.edu.au.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Despite intensive efforts to optimize the process, reprogramming differentiated cells to induced pluripotent stem cells (iPSCs) remains inefficient. The most common combination of transcription factors employed comprises OCT4, KLF4, SOX2, and MYC (OKSM). If MYC is omitted (OKS), reprogramming efficiency is reduced further. Cells must overcome several obstacles to reach the pluripotent state, one of which is apoptosis. To directly determine how extensively apoptosis limits reprogramming, we exploited mouse embryonic fibroblasts (MEFs) lacking the two essential mediators of apoptosis, BAK and BAX. Our results show that reprogramming is enhanced in MEFs deficient in BAK and BAX, but only when MYC is part of the reprogramming cocktail. Thus, the propensity for Myc overexpression to elicit apoptosis creates a significant roadblock to reprogramming under OKSM conditions. Our results suggest that blocking apoptosis during reprogramming may enhance the derivation of iPSCs for research and therapeutic purposes.

Indexed as

AnimalsApoptosisbcl-2-Associated X Proteinbcl-2 Homologous Antagonist-Killer ProteinCell DifferentiationCellular ReprogrammingFibroblastsGene Expression Regulation, DevelopmentalInduced Pluripotent Stem CellsKruppel-Like Factor 4MiceMouse Embryonic Stem CellsProto-Oncogene Proteins c-mycBak1 protein, mouseBax protein, mousebcl-2-Associated X Proteinbcl-2 Homologous Antagonist-Killer ProteinKlf4 protein, mouseKruppel-Like Factor 4Proto-Oncogene Proteins c-mycBAKBAXinduced pluripotent stem cellsmitochondrial apoptosismouse embryonic fibroblasts: reprogrammingMYCp53

Identifiers

PMID29358089
PMCPMC5830948

What OpenQuestion holds

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LicenceCC BY-NC-ND
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Registered trials

None linked

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.