Evidence map›Paper›PMID 26947976›Full record

ArticleStem cell reports2016

A Serial shRNA Screen for Roadblocks to Reprogramming Identifies the Protein Modifier SUMO2.

Marti Borkent, Brian D Bennett, Brad Lackford, Ori Bar-Nur, Justin Brumbaugh, Li Wang, Ying Du, David C Fargo, Effie Apostolou, Sihem Cheloufi and 4 more

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

Article in Stem cell reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed
4.4field-weighted citation impact, top 5% 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

37 citing papers in PubMed, 61 citations in OpenAlex.

  1. Article
  2. Regulation of lineage reprogramming by dynamic chromatin SUMOylation.Cellular and molecular life sciences : CMLS · 2026
    Article
  3. Article
  4. Review
  5. Review
  6. Article
  7. Review
  8. In Vitro Embryogenesis and Gastrulation Using Stem Cells in Mice and Humans.International journal of molecular sciences · 2023
    Review
  9. Review
  10. Article
  11. Article
  12. Protein sumoylation in normal and cancer stem cells.Frontiers in molecular biosciences · 2022
    Review
  13. Article
  14. The transcription factor code in iPSC reprogramming.Current opinion in genetics & development · 2021
    Review
  15. Article
  16. Article
  17. Article
  18. Article
  19. Review
  20. 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

14 authors at 4 institutions in 1 country.

Marti BorkentDepartment of Molecular Biology, Center for Regenerative Medicine and Cancer Center, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.
Brian D BennettIntegrative Bioinformatics, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA.
Brad LackfordEpigenetics and Stem Cell Biology Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA.
Ori Bar-NurDepartment of Molecular Biology, Center for Regenerative Medicine and Cancer Center, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.
Justin BrumbaughDepartment of Molecular Biology, Center for Regenerative Medicine and Cancer Center, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.
Li WangEpigenetics and Stem Cell Biology Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA.
Ying DuIntegrative Bioinformatics, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA.
David C FargoIntegrative Bioinformatics, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA.
Effie ApostolouDepartment of Molecular Biology, Center for Regenerative Medicine and Cancer Center, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.
Sihem CheloufiDepartment of Molecular Biology, Center for Regenerative Medicine and Cancer Center, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.
Nimet MaheraliDepartment of Molecular Biology, Center for Regenerative Medicine and Cancer Center, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.
Stephen J ElledgeHoward Hughes Medical Institute, Chevy Chase, MD 20815, USA; Department of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Guang HuEpigenetics and Stem Cell Biology Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Electronic address: hug4@niehs.nih.gov.
Konrad HochedlingerDepartment of Molecular Biology, Center for Regenerative Medicine and Cancer Center, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA. Electronic address: khochedlinger@mgh.harvard.edu.
National Institute of Environmental Health Sciences · USMassachusetts General Hospital · USHarvard Stem Cell Institute · USHoward Hughes Medical Institute · US

Funding

Role of Pluripotency Factors in Pluripotent Stem Cells, Development and DiseaseZIAES102745 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI HU, GUANG · 2010 to 2025
$31.5M
Ubiquitin Mediated Proteolysis and Cell Cycle ControlR01AG011085 · NIA · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI JEFFREY W HARPER · 1993 to 2026
$10.9M
Transcription Factor Induced ReprogrammingR01HD058013 · NICHD · MASSACHUSETTS GENERAL HOSPITAL · PI HOCHEDLINGER, KONRAD · 2010 to 2019
$4.4M
Genetics of Cell Cycle &DNA Damage Regulation in YeastR37GM044664 · NIGMS · BRIGHAM AND WOMEN'S HOSPITAL · PI ELLEDGE, STEPHEN J · 2003 to 2012
$3.5M
GENETICS OF CELL CYCLE &DNA DAMAGE REGULATION IN YEASTR01GM044664 · NIGMS · BRIGHAM AND WOMEN'S HOSPITAL · PI ELLEDGE, STEPHEN J · 1990 to 2016
$2.0M
The regulatory role of chromatin interaction in pluripotency and differentiationF32HD078029 · NICHD · MASSACHUSETTS GENERAL HOSPITAL · PI BRUMBAUGH, JUSTIN · 2014 to 2016
$175k
NIA NIH HHS R01 AG011085NICHD NIH HHS F32 HD078029NICHD NIH HHS R01 HD058013NIEHS NIH HHS ZIA ES102745NIGMS NIH HHS R01 GM044664NIGMS NIH HHS R37 GM044664
6 · The paper itself

Abstract

The generation of induced pluripotent stem cells (iPSCs) from differentiated cells following forced expression of OCT4, KLF4, SOX2, and C-MYC (OKSM) is slow and inefficient, suggesting that transcription factors have to overcome somatic barriers that resist cell fate change. Here, we performed an unbiased serial shRNA enrichment screen to identify potent repressors of somatic cell reprogramming into iPSCs. This effort uncovered the protein modifier SUMO2 as one of the strongest roadblocks to iPSC formation. Depletion of SUMO2 both enhances and accelerates reprogramming, yielding transgene-independent, chimera-competent iPSCs after as little as 38 hr of OKSM expression. We further show that the SUMO2 pathway acts independently of exogenous C-MYC expression and in parallel with small-molecule enhancers of reprogramming. Importantly, suppression of SUMO2 also promotes the generation of human iPSCs. Together, our results reveal sumoylation as a crucial post-transcriptional mechanism that resists the acquisition of pluripotency from fibroblasts using defined factors.

Indexed as

Cell DifferentiationCellular ReprogrammingGene Expression Regulation, DevelopmentalHumansInduced Pluripotent Stem CellsKruppel-Like Factor 4Proto-Oncogene Proteins c-mycRNA, Small InterferingSmall Ubiquitin-Related Modifier ProteinsKLF4 protein, humanKruppel-Like Factor 4MYC protein, humanProto-Oncogene Proteins c-mycRNA, Small InterferingSmall Ubiquitin-Related Modifier ProteinsSUMO2 protein, human

Identifiers

PMID26947976
PMCPMC4939549
OpenAlexW2290873962

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.