Evidence map›Paper›PMID 25471879›Full record

ArticleNature2014

Deconstructing transcriptional heterogeneity in pluripotent stem cells.

Roshan M Kumar, Patrick Cahan, Alex K Shalek, Rahul Satija, AJay DaleyKeyser, Hu Li, Jin Zhang, Keith Pardee, David Gennert, John J Trombetta and 4 more

Abstract read
In one paragraph

Article in Nature, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 217 papers.

0numbers the graph read from it
0cells of the map it votes in
217citing 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

217 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Article
  6. Article
  7. Review
  8. CeiTEA: Adaptive Hierarchy of Single Cells with Topological Entropy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    Article
  9. Article
  10. Article
  11. Review
  12. Article
  13. Lung Immune Cell Niches and the Discovery of New Cell Subtypes.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024
    Review
  14. Review
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Review

157 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors.

Roshan M Kumar *Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, Massachusetts 02115, USA.
Patrick Cahan *Stem Cell Transplantation Program, Division of Pediatric Hematology and Oncology, Manton Center for Orphan Disease Research, Howard Hughes Medical Institute, Boston Children's Hospital and Dana Farber Cancer Institute, Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Harvard Stem Cell Institute, Boston, Massachusetts 02115, USA.
Alex K ShalekDepartment of Chemistry and Chemical Biology and Department of Physics, Harvard University, 12 Oxford Street, Cambridge, Massachusetts 02138, USA.
Rahul SatijaBroad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA.
AJay DaleyKeyserWyss Institute for Biologically Inspired Engineering, Harvard University, Boston, Massachusetts 02115, USA.
Hu LiCenter for Individualized Medicine, Department of Molecular Pharmacology & Experimental Therapeutics, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA.
Jin ZhangStem Cell Transplantation Program, Division of Pediatric Hematology and Oncology, Manton Center for Orphan Disease Research, Howard Hughes Medical Institute, Boston Children's Hospital and Dana Farber Cancer Institute, Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Harvard Stem Cell Institute, Boston, Massachusetts 02115, USA.
Keith PardeeWyss Institute for Biologically Inspired Engineering, Harvard University, Boston, Massachusetts 02115, USA.
David GennertBroad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA.
John J TrombettaBroad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA.
Thomas C FerranteWyss Institute for Biologically Inspired Engineering, Harvard University, Boston, Massachusetts 02115, USA.
Aviv RegevBroad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA.
George Q DaleyStem Cell Transplantation Program, Division of Pediatric Hematology and Oncology, Manton Center for Orphan Disease Research, Howard Hughes Medical Institute, Boston Children's Hospital and Dana Farber Cancer Institute, Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Harvard Stem Cell Institute, Boston, Massachusetts 02115, USA.
James J CollinsWyss Institute for Biologically Inspired Engineering, Harvard University, Boston, Massachusetts 02115, USA.

Funding

SYNAPTIC MECHANISMS IN HIPPOCAMPAL EPILEPTOGENESISP30HD018655 · NICHD · CHILDREN'S HOSPITAL BOSTON · PI FAGIOLINI, MICHELA · 1985 to 2015
$26.2M
Causal Transcriptional Consequences of Human Genetic VariationP50HG005550 · NHGRI · HARVARD MEDICAL SCHOOL · PI CHURCH, GEORGE M · 2010 to 2014
$19.0M
Center for Cell CircuitsP50HG006193 · NHGRI · BROAD INSTITUTE, INC. · PI REGEV, AVIV · 2011 to 2015
$15.6M
Customized stem cells for clinical application in blood disordersR24DK092760 · NIDDK · BOSTON CHILDREN'S HOSPITAL · PI COLLINS, JAMES J, DALEY, GEORGE Q · 2011 to 2018
$10.7M
TRANSFUSION BIOLOGY AND MEDICINET32HL066987 · NHLBI · CHILDREN'S HOSPITAL BOSTON · PI JOHN P MANIS · 2001 to 2026
$10.2M
TRAINING PROGRAM IN MOLECULAR HEMATOLOGYT32HL007623 · NHLBI · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI HANDIN, ROBERT I · 1985 to 2010
$7.0M
The temporal reconfiguration of regulatory networks: From yeast to cancerDP1OD003958 · OD · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI REGEV, AVIV · 2008 to 2011
$3.3M
Understanding the role of the lin28 paralogs and branching morphogenesisR01GM107536 · NIGMS · BOSTON CHILDREN'S HOSPITAL · PI DALEY, GEORGE Q · 2014 to 2017
$1.9M
The temporal reconfiguration of regulatory networks: From yeast to cancerDP1CA174427 · NCI · BROAD INSTITUTE, INC. · PI REGEV, AVIV · 2012 to 2012
$839k
Pluripotent stem cell-derived HSCs: improvements and molecular mechanismsK01DK096013 · NIDDK · JOHNS HOPKINS UNIVERSITY · PI CAHAN, PATRICK · 2013 to 2017
$781k
The chromatin regulatory circuitry of bivalent domainsF32HD075541 · NICHD · BROAD INSTITUTE, INC. · PI SATIJA, RAHUL · 2013 to 2014
$99k
Howard Hughes Medical InstituteNCI NIH HHS DP1 CA174427NHGRI NIH HHS P50 HG005550NHGRI NIH HHS P50 HG006193NHLBI NIH HHS T32 HL007623NHLBI NIH HHS T32 HL066987NICHD NIH HHS F32 HD075541NICHD NIH HHS P30 HD018655NIDDK NIH HHS K01 DK096013NIDDK NIH HHS R24 DK092760NIGMS NIH HHS R01 GM107536NIH HHS DP1 OD003958
6 · The paper itself

Abstract

Pluripotent stem cells (PSCs) are capable of dynamic interconversion between distinct substates; however, the regulatory circuits specifying these states and enabling transitions between them are not well understood. Here we set out to characterize transcriptional heterogeneity in mouse PSCs by single-cell expression profiling under different chemical and genetic perturbations. Signalling factors and developmental regulators show highly variable expression, with expression states for some variable genes heritable through multiple cell divisions. Expression variability and population heterogeneity can be influenced by perturbation of signalling pathways and chromatin regulators. Notably, either removal of mature microRNAs or pharmacological blockage of signalling pathways drives PSCs into a low-noise ground state characterized by a reconfigured pluripotency network, enhanced self-renewal and a distinct chromatin state, an effect mediated by opposing microRNA families acting on the Myc/Lin28/let-7 axis. These data provide insight into the nature of transcriptional heterogeneity in PSCs.

Indexed as

Gene Expression Regulation, DevelopmentalAnimalsCell DeathCell DivisionEmbryonic Stem CellsGene Expression ProfilingMiceMicroRNAsPluripotent Stem CellsSignal TransductionMicroRNAs

Identifiers

PMID25471879
PMCPMC4256722

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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.