Evidence map›Paper›PMID 25336442›Full record

ArticleStem cells (Dayton, Ohio)2015

Interrogation of a context-specific transcription factor network identifies novel regulators of pluripotency.

Ritu Kushwaha, Nirmala Jagadish, Manjunath Kustagi, Mark J Tomishima, Geetu Mendiratta, Mukesh Bansal, Hyunjae R Kim, Pavel Sumazin, Mariano J Alvarez, Celine Lefebvre and 8 more

Open access · bronzeAbstract read
In one paragraph

Article in Stem cells (Dayton, Ohio), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
2.1field-weighted citation impact, top 13% 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

21 citing papers in PubMed, 38 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Bioengineered · 2022
    Article
  6. Article
  7. Article
  8. Racial Differences in the Association Between Luminal Master Regulator Gene Expression Levels and Breast Cancer Survival.Clinical cancer research : an official journal of the American Association for Cancer Research · 2020
    Article
  9. Impact of Teratoma on the Cumulative Incidence of Disease-Related Death in Patients With Advanced Germ Cell Tumors.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2019
    Article
  10. Article
  11. Article
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  15. Article
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  17. Review
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  19. Article
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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

18 authors at 2 institutions in 1 country.

Ritu KushwahaCell Biology Program, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.
Nirmala Jagadish
Manjunath Kustagi
Mark J Tomishima
Geetu Mendiratta
Mukesh Bansal
Hyunjae R Kim
Pavel Sumazin
Mariano J Alvarez
Celine Lefebvre
Patricia Villagrasa-Gonzalez
Agnes Viale
James E Korkola
Jane Houldsworth
Darren R Feldman
George J Bosl
Andrea Califano
R S K Chaganti
Memorial Sloan Kettering Cancer Center · USColumbia University · US

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Nicholas D Socci · 1985 to 2026
$347.4M
Nation Center: Multi-Scale Study- Cellular Networks(RMI)U54CA121852 · NCI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI CALIFANO, ANDREA · 2005 to 2015
$37.4M
Predicting Cancer Cell Response to Endogenous and Exogenous Perturbations at the Single Cell LevelR35CA197745 · NCI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI ANDREA CALIFANO · 2015 to 2026
$11.5M
Genetic Network Inference with Combinational PhenotypesR01CA109755 · NCI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI CALIFANO, ANDREA · 2005 to 2009
$1.9M
Identification of Master Regulators for stem cell pluripotency and self-renewalRC1GM091240 · NIGMS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI CALIFANO, ANDREA, SHEN, MICHAEL M. · 2010 to 2010
$997k
NCI NIH HHS CA008748NCI NIH HHS CA109755NCI NIH HHS CA121852NCI NIH HHS P30 CA008748NCI NIH HHS R01 CA109755NCI NIH HHS R35 CA197745NCI NIH HHS U54 CA121852NIGMS NIH HHS GM091240NIGMS NIH HHS RC1 GM091240
6 · The paper itself

Abstract

The predominant view of pluripotency regulation proposes a stable ground state with coordinated expression of key transcription factors (TFs) that prohibit differentiation. Another perspective suggests a more complexly regulated state involving competition between multiple lineage-specifying TFs that define pluripotency. These contrasting views were developed from extensive analyses of TFs in pluripotent cells in vitro. An experimentally validated, genome-wide repertoire of the regulatory interactions that control pluripotency within the in vivo cellular contexts is yet to be developed. To address this limitation, we assembled a TF interactome of adult human male germ cell tumors (GCTs) using the Algorithm for the Accurate Reconstruction of Cellular Pathways (ARACNe) to analyze gene expression profiles of 141 tumors comprising pluripotent and differentiated subsets. The network (GCT(Net)) comprised 1,305 TFs, and its ingenuity pathway analysis identified pluripotency and embryonal development as the top functional pathways. We experimentally validated GCT(Net) by functional (silencing) and biochemical (ChIP-seq) analysis of the core pluripotency regulatory TFs POU5F1, NANOG, and SOX2 in relation to their targets predicted by ARACNe. To define the extent of the in vivo pluripotency network in this system, we ranked all TFs in the GCT(Net) according to sharing of ARACNe-predicted targets with those of POU5F1 and NANOG using an odds-ratio analysis method. To validate this network, we silenced the top 10 TFs in the network in H9 embryonic stem cells. Silencing of each led to downregulation of pluripotency and induction of lineage; 7 of the 10 TFs were identified as pluripotency regulators for the first time.

Indexed as

AlgorithmsModels, BiologicalAdultCell Line, TumorHumansMaleNeoplasm ProteinsNeoplasms, Germ Cell and EmbryonalPluripotent Stem CellsTranscription FactorsNeoplasm ProteinsTranscription FactorsBiomathematical modelingDifferentiationEmbryonal carcinomaEmbryonic stem cellsGene expressionPluripotent stem cells

Identifiers

PMID25336442
PMCPMC4305010
OpenAlexW1763220019

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.