Evidence map›Paper›PMID 38956165›Full record

ArticleNature neuroscience2024

Direct neuronal reprogramming of mouse astrocytes is associated with multiscale epigenome remodeling and requires Yy1.

Allwyn Pereira, Jeisimhan Diwakar, Giacomo Masserdotti, Sude Beşkardeş, Tatiana Simon, Younju So, Lucía Martín-Loarte, Franziska Bergemann, Lakshmy Vasan, Tamas Schauer and 8 more

Abstract read
In one paragraph

Article in Nature neuroscience, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing 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

26 citing papers in PubMed.

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  8. Phosphorylation and DNA damage resolution coordinate SOX2-mediated reprogramming in vivo.Proceedings of the National Academy of Sciences of the United States of America · 2026
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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.

Allwyn PereiraBiomedical Center Munich (BMC), Physiological Genomics, LMU Munich, Planegg, Germany.ORCID http://orcid.org/0000-0003-3825-4359
Jeisimhan Diwakar *Biomedical Center Munich (BMC), Physiological Genomics, LMU Munich, Planegg, Germany.ORCID http://orcid.org/0000-0002-9520-6823
Giacomo Masserdotti *Biomedical Center Munich (BMC), Physiological Genomics, LMU Munich, Planegg, Germany.ORCID http://orcid.org/0000-0003-3621-3481
Sude BeşkardeşBiomedical Center Munich (BMC), Physiological Genomics, LMU Munich, Planegg, Germany.
Tatiana SimonBiomedical Center Munich (BMC), Physiological Genomics, LMU Munich, Planegg, Germany.
Younju SoBiomedical Center Munich (BMC), Physiological Genomics, LMU Munich, Planegg, Germany.
Lucía Martín-LoarteBiomedical Center Munich (BMC), Physiological Genomics, LMU Munich, Planegg, Germany.
Franziska BergemannBiomedical Center Munich (BMC), Physiological Genomics, LMU Munich, Planegg, Germany.
Lakshmy VasanBiological Science Platform, Sunnybrook Research Institute; Department of Biochemistry, University of Toronto, Toronto, ON, Canada.
Tamas SchauerBiomedical Center Munich (BMC), Bioinformatic Core Facility, Faculty of Medicine, LMU Munich, Planegg, Germany.
Anna DaneseBiomedical Center Munich (BMC), Physiological Genomics, LMU Munich, Planegg, Germany.
Riccardo BocchiBiomedical Center Munich (BMC), Physiological Genomics, LMU Munich, Planegg, Germany.ORCID http://orcid.org/0000-0002-4105-6807
Maria Colomé-TatchéInstitute of Computational Biology, Helmholtz Center Munich, Neuherberg, Germany.
Carol SchuurmansBiological Science Platform, Sunnybrook Research Institute; Department of Biochemistry, University of Toronto, Toronto, ON, Canada.
Anna PhilpottWellcome-Medical Research Council Cambridge Stem Cell Institute, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK.
Tobias StraubBiological Science Platform, Sunnybrook Research Institute; Department of Biochemistry, University of Toronto, Toronto, ON, Canada.
Boyan BonevBiomedical Center Munich (BMC), Physiological Genomics, LMU Munich, Planegg, Germany. boyan.bonev@helmholtz-munich.de.ORCID http://orcid.org/0000-0002-7502-9399
Magdalena GötzBiomedical Center Munich (BMC), Physiological Genomics, LMU Munich, Planegg, Germany. magdalena.goetz@helmholtz-munich.de.ORCID http://orcid.org/0000-0003-1551-9203

Funding

Medical Research Council MC_PC_17230Wellcome Trust
6 · The paper itself

Abstract

Direct neuronal reprogramming is a promising approach to regenerate neurons from local glial cells. However, mechanisms of epigenome remodeling and co-factors facilitating this process are unclear. In this study, we combined single-cell multiomics with genome-wide profiling of three-dimensional nuclear architecture and DNA methylation in mouse astrocyte-to-neuron reprogramming mediated by Neurogenin2 (Ngn2) and its phosphorylation-resistant form (PmutNgn2), respectively. We show that Ngn2 drives multilayered chromatin remodeling at dynamic enhancer-gene interaction sites. PmutNgn2 leads to higher reprogramming efficiency and enhances epigenetic remodeling associated with neuronal maturation. However, the differences in binding sites or downstream gene activation cannot fully explain this effect. Instead, we identified Yy1, a transcriptional co-factor recruited by direct interaction with Ngn2 to its target sites. Upon deletion of Yy1, activation of neuronal enhancers, genes and ultimately reprogramming are impaired without affecting Ngn2 binding. Thus, our work highlights the key role of interactors of proneural factors in direct neuronal reprogramming.

Indexed as

AstrocytesBasic Helix-Loop-Helix ProteinsCellular ReprogrammingNerve Tissue ProteinsNeuronsYY1 Transcription FactorAnimalsCells, CulturedChromatin Assembly and DisassemblyEpigenesis, GeneticEpigenomeMiceBasic Helix-Loop-Helix ProteinsNerve Tissue ProteinsNeurog2 protein, mouseYy1 protein, mouseYY1 Transcription Factor

Identifiers

PMID38956165
PMCPMC11239498

What OpenQuestion holds

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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.