Evidence map›Paper›PMID 26119235›Full record

ArticleCell stem cell2015

Transcriptional Mechanisms of Proneural Factors and REST in Regulating Neuronal Reprogramming of Astrocytes.

Giacomo Masserdotti, Sébastien Gillotin, Bernd Sutor, Daniela Drechsel, Martin Irmler, Helle F Jørgensen, Steffen Sass, Fabian J Theis, Johannes Beckers, Benedikt Berninger and 2 more

Open access · hybridAbstract read
In one paragraph

Article in Cell stem cell, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 113 papers.

0numbers the graph read from it
0cells of the map it votes in
113citing papers in PubMed
8.3field-weighted citation impact, top 2% 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

113 citing papers in PubMed, 195 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Review
  6. Article
  7. Article
  8. Article
  9. Review
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors at 7 institutions in 2 countries.

Giacomo MasserdottiPhysiological Genomics, Biomedical Center, University of Munich, 80336 Munich, Germany; Institute for Stem Cell Research, Helmholtz Centre Munich, 85764 Neuherberg, Germany.
Sébastien GillotinThe Francis Crick Institute, Mill Hill Laboratory, The Ridgeway, London, NW7 1AA, UK; Hutchison/MRC Research Center, University of Cambridge, Cambridge Biomedical Campus, Cambridge, CB2 0XZ, UK.
Bernd SutorPhysiological Genomics, Biomedical Center, University of Munich, 80336 Munich, Germany.
Daniela DrechselThe Francis Crick Institute, Mill Hill Laboratory, The Ridgeway, London, NW7 1AA, UK.
Martin IrmlerInstitute of Experimental Genetics, Helmholtz Centre Munich, 85764 Neuherberg, Germany.
Helle F JørgensenDepartment of Medicine, University of Cambridge, Cambridge, CB2 0QQ, UK.
Steffen SassInstitute of Computational Biology, Helmholtz Centre Munich, 85764 Neuherberg, Germany.
Fabian J TheisInstitute of Computational Biology, Helmholtz Centre Munich, 85764 Neuherberg, Germany; Department of Mathematics, Technical University Munich, 85748 Garching, Germany.
Johannes BeckersInstitute of Experimental Genetics, Helmholtz Centre Munich, 85764 Neuherberg, Germany; Center of Life and Food Sciences Weihenstephan, Technical University, 85354 Freising, Germany.
Benedikt BerningerInstitute of Physiological Chemistry, University Medical Center of the Johannes Gutenberg University, D-55128 Mainz, Germany; Focus Program Translational Neuroscience, Johannes Gutenberg University, D-55128 Mainz, Germany.
François GuillemotThe Francis Crick Institute, Mill Hill Laboratory, The Ridgeway, London, NW7 1AA, UK. Electronic address: francois.guillemot@crick.ac.uk.
Magdalena GötzPhysiological Genomics, Biomedical Center, University of Munich, 80336 Munich, Germany; Institute for Stem Cell Research, Helmholtz Centre Munich, 85764 Neuherberg, Germany; Munich Cluster for Systems Neurology "SyNergy," Ludwig Maximilian University of Munich, 80539 Munich, Germany. Electronic address: magdalena.goetz@helmholtz-muenchen.de.
Helmholtz Zentrum München · DEThe Francis Crick Institute · GBLudwig-Maximilians-Universität München · DETechnical University of Munich · DEUniversity Medical Center of the Johannes Gutenberg University Mainz · DEUniversity of Cambridge · GBWeihenstephan-Triesdorf University of Applied Sciences · DE

Funding

Medical Research Council G0800784Medical Research Council G1000847Medical Research Council MC_U117570528Medical Research Council U117570528Wellcome TrustWellcome Trust WT091800MA
6 · The paper itself

Abstract

Direct lineage reprogramming induces dramatic shifts in cellular identity, employing poorly understood mechanisms. Recently, we demonstrated that expression of Neurog2 or Ascl1 in postnatal mouse astrocytes generates glutamatergic or GABAergic neurons. Here, we take advantage of this model to study dynamics of neuronal cell fate acquisition at the transcriptional level. We found that Neurog2 and Ascl1 rapidly elicited distinct neurogenic programs with only a small subset of shared target genes. Within this subset, only NeuroD4 could by itself induce neuronal reprogramming in both mouse and human astrocytes, while co-expression with Insm1 was required for glutamatergic maturation. Cultured astrocytes gradually became refractory to reprogramming, in part by the repressor REST preventing Neurog2 from binding to the NeuroD4 promoter. Notably, in astrocytes refractory to Neurog2 activation, the underlying neurogenic program remained amenable to reprogramming by exogenous NeuroD4. Our findings support a model of temporal hierarchy for cell fate change during neuronal reprogramming.

Indexed as

AnimalsAstrocytesBasic Helix-Loop-Helix ProteinsCells, CulturedCellular ReprogrammingDNA-Binding ProteinsHumansMiceNerve Tissue ProteinsNeuronsPromoter Regions, GeneticRE1-Silencing Transcription FactorRepressor ProteinsTranscription FactorsTranscription, GeneticAscl1 protein, mouseBasic Helix-Loop-Helix ProteinsDNA-Binding ProteinsInsm1 protein, mouseNerve Tissue ProteinsNeurod4 protein, mouseNeurog2 protein, mouseRE1-Silencing Transcription FactorRepressor ProteinsTranscription Factors

Identifiers

PMID26119235
PMCPMC4509553
OpenAlexW1836539731

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.