Evidence map›Paper›PMID 23995732›Full record

ArticleNature cell biology2013

Early role for IL-6 signalling during generation of induced pluripotent stem cells revealed by heterokaryon RNA-Seq.

Jennifer J Brady, Mavis Li, Silpa Suthram, Hui Jiang, Wing H Wong, Helen M Blau

Open access · greenAbstract read
In one paragraph

Article in Nature cell biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.

0numbers the graph read from it
0cells of the map it votes in
56citing papers in PubMed
2.7field-weighted citation impact, top 10% of its field
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

56 citing papers in PubMed, 97 citations in OpenAlex.

  1. A cross-talk between p16High senescence and cellular reprogramming.Clinical science (London, England : 1979) · 2026
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  9. Super-enhancers conserved within placental mammals maintain stem cell pluripotency.Proceedings of the National Academy of Sciences of the United States of America · 2022
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  14. Clearance of Senescent Cells From Injured Muscle Abrogates Heterotopic Ossification in Mouse Models of Fibrodysplasia Ossificans Progressiva.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2022
    Article
  15. Review
  16. Cytokines That Serve as Embryokines in Cattle.Animals : an open access journal from MDPI · 2021
    Review
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  18. AP-1 is a temporally regulated dual gatekeeper of reprogramming to pluripotency.Proceedings of the National Academy of Sciences of the United States of America · 2021
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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

6 authors at 2 institutions in 1 country.

Jennifer J BradyBaxter Laboratory for Stem Cell Biology, Department of Microbiology and Immunology, Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, California 94305, USA.
Mavis Li
Silpa Suthram
Hui Jiang
Wing H Wong
Helen M Blau
Stanford University · USBaxter (United States) · US

Funding

Basic and Translational Research iPSC-based hematologic and vascular therapiesU01HL100397 · NHLBI · STANFORD UNIVERSITY · PI COOKE, JOHN P · 2009 to 2015
$7.4M
Stem Cells for Brain and BrawnR01AG020961 · NIA · STANFORD UNIVERSITY · PI BLAU, HELEN M · 2002 to 2019
$5.0M
ACTIVATORS OF MUSCLE GENESR01AG009521 · NIA · STANFORD UNIVERSITY · PI BLAU, HELEN M · 1990 to 2014
$4.7M
Regulation of Hematopoietic Stem Cell Fate in Bioengineered NichesR01HL096113 · NHLBI · STANFORD UNIVERSITY · PI BLAU, HELEN M · 2009 to 2013
$2.7M
Regulator of Adult Stem Cell FateR01AG024987 · NIA · STANFORD UNIVERSITY · PI BLAU, HELEN M · 2004 to 2008
$1.7M
An approach to gene regulatory network inference.R01HG006018 · NHGRI · STANFORD UNIVERSITY · PI WONG, WING H. · 2011 to 2013
$1.1M
Statistical analysis of RNA-Seq dataR01HG005717 · NHGRI · STANFORD UNIVERSITY · PI WONG, WING H. · 2011 to 2013
$1.1M
NHGRI NIH HHS HG006018NHGRI NIH HHS R01 HG005717NHGRI NIH HHS R01 HG006018NHLBI NIH HHS R01 HL096113NHLBI NIH HHS U01 HL100397NIA NIH HHS R01 AG009521NIA NIH HHS R01 AG020961NIA NIH HHS R01 AG024987
6 · The paper itself

Abstract

Molecular insights into somatic cell reprogramming to induced pluripotent stem cells (iPS) would aid regenerative medicine, but are difficult to elucidate in iPS because of their heterogeneity, as relatively few cells undergo reprogramming (0.1-1%; refs , ). To identify early acting regulators, we capitalized on non-dividing heterokaryons (mouse embryonic stem cells fused to human fibroblasts), in which reprogramming towards pluripotency is efficient and rapid, enabling the identification of transient regulators required at the onset. We used bi-species transcriptome-wide RNA-seq to quantify transcriptional changes in the human somatic nucleus during reprogramming towards pluripotency in heterokaryons. During heterokaryon reprogramming, the cytokine interleukin 6 (IL6), which is not detectable at significant levels in embryonic stem cells, was induced 50-fold. A 4-day culture with IL6 at the onset of iPS reprogramming replaced stably transduced oncogenic c-Myc such that transduction of only Oct4, Klf4 and Sox2 was required. IL6 also activated another Jak/Stat target, the serine/threonine kinase gene Pim1, which accounted for the IL6-mediated twofold increase in iPS frequency. In contrast, LIF, another induced GP130 ligand, failed to increase iPS frequency or activate c-Myc or Pim1, thereby revealing a differential role for the two Jak/Stat inducers in iPS generation. These findings demonstrate the power of heterokaryon bi-species global RNA-seq to identify early acting regulators of reprogramming, for example, extrinsic replacements for stably transduced transcription factors such as the potent oncogene c-Myc.

Indexed as

Signal TransductionAnimalsCellular ReprogrammingCytokine Receptor gp130Embryonic Stem CellsFungal ProteinsGene Expression ProfilingGene Expression RegulationHumansInduced Pluripotent Stem CellsInterleukin-6Kruppel-Like Factor 4MaleMiceMitogen-Activated Protein KinasesMolecular Sequence DataCytokine Receptor gp130Fungal ProteinsInterleukin-6KLF4 protein, humanKlf4 protein, mouseKruppel-Like Factor 4Mitogen-Activated Protein KinasesPim1 protein, Pichia pastoris

Identifiers

PMID23995732
PMCPMC4100556
OpenAlexW2031022464

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

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.