Evidence map›Paper›PMID 25666918›Full record

ArticleMolecular therapy : the journal of the American Society of Gene Therapy2015

cAMP and EPAC Signaling Functionally Replace OCT4 During Induced Pluripotent Stem Cell Reprogramming.

Ashley L Fritz, Maroof M Adil, Sunnie R Mao, David V Schaffer

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
1.1field-weighted citation impact, top 24% 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

14 citing papers in PubMed, 25 citations in OpenAlex.

  1. Article
  2. Rat embryonic stem cell-basedFrontiers in toxicology · 2025
    Article
  3. Article
  4. Review
  5. Review
  6. Article
  7. Article
  8. Article
  9. cAMP/EPAC Signaling Enables ETV2 to Induce Endothelial Cells with High Angiogenesis Potential.Molecular therapy : the journal of the American Society of Gene Therapy · 2020
    Article
  10. Article
  11. Review
  12. Article
  13. Article
  14. 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

4 authors at 1 institution in 1 country.

Ashley L FritzDepartment of Chemical and Biomolecular Engineering, University of California, Berkeley, California, USA.
Maroof M AdilDepartment of Chemical and Biomolecular Engineering, University of California, Berkeley, California, USA.
Sunnie R MaoDepartment of Chemical and Biomolecular Engineering, University of California, Berkeley, California, USA.
David V SchafferDepartment of Chemical and Biomolecular Engineering, University of California, Berkeley, California, USA; Department of Bioengineering, University of California, Berkeley, California, USA; Helen Wills Neuroscience Institute, University of California, Berkeley, California, USA. Electronic address: schaffer@berkeley.edu.
University of California, Berkeley · US

Funding

High-Throughput Platform for Identifying Stem Cell ToxicityR01ES020903 · NIEHS · RENSSELAER POLYTECHNIC INSTITUTE · PI DORDICK, JONATHAN S., SCHAFFER, DAVID V · 2012 to 2015
$2.0M
NIEHS NIH HHS NIH R01 ES020903NIEHS NIH HHS R01 ES020903
6 · The paper itself

Abstract

The advent of induced pluripotent stem cells--generated via the ectopic overexpression of reprogramming factors such as OCT4, SOX2, KLF4, and C-MYC (OSKM) in a differentiated cell type--has enabled groundbreaking research efforts in regenerative medicine, disease modeling, and drug discovery. Although initial studies have focused on the roles of nuclear factors, increasing evidence highlights the importance of signal transduction during reprogramming. By utilizing a quantitative, medium-throughput screen to initially identify signaling pathways that could potentially replace individual transcription factors during reprogramming, we initially found that several pathways--such as Notch, Smoothened, and cyclic AMP (cAMP) signaling--were capable of generating alkaline phosphatase positive colonies in the absence of OCT4, the most stringently required Yamanaka factor. After further investigation, we discovered that cAMP signal activation could functionally replace OCT4 to induce pluripotency, and results indicate that the downstream exchange protein directly activated by cAMP (EPAC) signaling pathway rather than protein kinase A (PKA) signaling is necessary and sufficient for this function. cAMP signaling may reduce barriers to reprogramming by contributing to downstream epithelial gene expression, decreasing mesenchymal gene expression, and increasing proliferation. Ultimately, these results elucidate mechanisms that could lead to new reprogramming methodologies and advance our understanding of stem cell biology.

Indexed as

Cellular ReprogrammingSignal TransductionAdenylyl CyclasesAlkaline PhosphataseCell DivisionColforsinColony-Forming Units AssayCyclic AMPEpithelial-Mesenchymal TransitionGuanine Nucleotide Exchange FactorsHumansInduced Pluripotent Stem CellsKruppel-Like Factor 4Octamer Transcription Factor-3Transcription, GeneticTransgenesAdenylyl CyclasesAlkaline PhosphataseColforsinCyclic AMPGuanine Nucleotide Exchange FactorsKLF4 protein, humanKruppel-Like Factor 4Octamer Transcription Factor-3RAPGEF3 protein, human

Identifiers

PMID25666918
PMCPMC4427878
OpenAlexW1984537581

What OpenQuestion holds

Textmetadata
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.