Evidence map›Paper›PMID 29551301›Full record

ArticleCell stem cell2018

Dissecting the Functional Consequences of De Novo DNA Methylation Dynamics in Human Motor Neuron Differentiation and Physiology.

Michael J Ziller, Juan A Ortega, Katharina A Quinlan, David P Santos, Hongcang Gu, Eric J Martin, Christina Galonska, Ramona Pop, Susanne Maidl, Alba Di Pardo and 6 more

Open access · bronzeAbstract read
In one paragraph

Article in Cell stem cell, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.

0numbers the graph read from it
0cells of the map it votes in
51citing papers in PubMed
3.6field-weighted citation impact, top 6% 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

51 citing papers in PubMed, 85 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Peptide Electrostatic Modulation Directs Human Neural Cell Fate.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  7. Laser Capture Microdissection Followed by DNA Methylation Profiling.Methods in molecular biology (Clifton, N.J.) · 2026
    Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Review
  13. MCL-1 regulates cellular transitions during oligodendrocyte development.bioRxiv : the preprint server for biology · 2024
    Article
  14. Article
  15. Review
  16. Review
  17. Review
  18. Article
  19. Article
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

16 authors at 6 institutions in 2 countries.

Michael J ZillerDepartment of Translational Psychiatry, Max Planck Institute of Psychiatry, Munich 80804, Germany.
Juan A OrtegaThe Ken & Ruth Davee Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Katharina A QuinlanDepartment of Biomedical and Pharmaceutical Sciences, George and Anne Ryan Institute for Neuroscience, University of Rhode Island, Kingston, RI 02881, USA.
David P SantosThe Ken & Ruth Davee Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Hongcang GuBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Eric J MartinThe Ken & Ruth Davee Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Christina GalonskaDepartment of Genome Regulation, Max Planck Institute for Molecular Genetics, Berlin 14195, Germany.
Ramona PopDepartment of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.
Susanne MaidlDepartment of Translational Psychiatry, Max Planck Institute of Psychiatry, Munich 80804, Germany.
Alba Di PardoThe Ken & Ruth Davee Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Mei HuangDepartment of Psychiatry and Behavioral Sciences, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Herbert Y MeltzerDepartment of Psychiatry and Behavioral Sciences, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA; Department of Physiology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Andreas GnirkeBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
C J HeckmanDepartment of Physiology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Alexander MeissnerBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Genome Regulation, Max Planck Institute for Molecular Genetics, Berlin 14195, Germany; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA. Electronic address: meissner@molgen.mpg.de.
Evangelos KiskinisThe Ken & Ruth Davee Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA; Department of Physiology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA. Electronic address: evangelos.kiskinis@northwestern.edu.
Northwestern University · USBroad Institute · USMax Planck Institute of Psychiatry · DEHarvard University · USMax Planck Institute for Molecular Genetics · DEUniversity of Rhode Island · US

Funding

Regulatory Roles and Dynamics of Nuclear long-noncoding RNAs in PluripotencyP01GM099117 · NIGMS · HARVARD UNIVERSITY · PI MEISSNER, ALEXANDER · 2011 to 2021
$21.2M
Center for Cell CircuitsP50HG006193 · NHGRI · BROAD INSTITUTE, INC. · PI REGEV, AVIV · 2011 to 2015
$15.6M
Determining How Defective Nucleo-Cytoplasmic Trafficking Leads To Neurodegeneration In C9orf72-Related ALS And FTDR01NS104219 · NINDS · NORTHWESTERN UNIVERSITY AT CHICAGO · PI KISKINIS, EVANGELOS · 2018 to 2022
$2.3M
Generation and characterization of tools for target-specific de novo DNA methylatR01DA036898 · NIDA · HARVARD UNIVERSITY · PI MEISSNER, ALEXANDER · 2013 to 2017
$1.7M
NHGRI NIH HHS P50 HG006193NIDA NIH HHS R01 DA036898NIGMS NIH HHS P01 GM099117NINDS NIH HHS R01 NS104219
6 · The paper itself

Abstract

The somatic DNA methylation (DNAme) landscape is established early in development but remains highly dynamic within focal regions that overlap with gene regulatory elements. The significance of these dynamic changes, particularly in the central nervous system, remains unresolved. Here, we utilize a powerful human embryonic stem cell differentiation model for the generation of motor neurons (MNs) in combination with genetic mutations in the de novo DNAme machinery. We quantitatively dissect the role of DNAme in directing somatic cell fate with high-resolution genome-wide bisulfite-, bulk-, and single-cell-RNA sequencing. We find defects in neuralization and MN differentiation in DNMT3A knockouts (KO) that can be rescued by the targeting of DNAme to key developmental loci using catalytically inactive dCas9. We also find decreased dendritic arborization and altered electrophysiological properties in DNMT3A KO MNs. Our work provides a list of DNMT3A-regulated targets and a mechanistic link between de novo DNAme, cellular differentiation, and human MN function.

Indexed as

Cell DifferentiationDNA MethylationBiocatalysisDNA (Cytosine-5-)-MethyltransferasesDNA Methyltransferase 3AHumansMotor NeuronsDNA (Cytosine-5-)-MethyltransferasesDNA Methyltransferase 3ADNMT3A protein, humancell fateDNA methylationDNMT3AepigeneticsESCsmotor neuronsneurogenesisspinal cord development

Identifiers

PMID29551301
PMCPMC6535433
OpenAlexW2792349974

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.