Evidence map›Paper›PMID 38561465›Full record

ArticleMolecular psychiatry2024

Differential DNA methylation in iPSC-derived dopaminergic neurons: a step forward on the role of SNORD116 microdeletion in the pathophysiology of addictive behavior in Prader-Willi syndrome.

Juliette Salles, Sanaa Eddiry, Saber Amri, Mélissa Galindo, Emmanuelle Lacassagne, Simon George, Xavier Mialhe, Émeline Lhuillier, Nicolas Franchitto, Freddy Jeanneteau and 3 more

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Article in Molecular psychiatry, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.6field-weighted citation impact, top 30% 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

4 citing papers in PubMed, 1 citations in OpenAlex.

  1. Review
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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

13 authors at 3 institutions in 3 countries.

Juliette SallesService de psychiatrie d'urgences, de crise et de liaison; Institut des Handicaps Neurologiques, Psychiatriques et Sensoriels, CHU de Toulouse; Infinity Center, Inserm CNRS UMR1291, University of Toulouse 3 Paul Sabatier, Toulouse, France. juliette.salles@hotmail.fr.ORCID 0000-0002-4497-8006
Sanaa EddiryEndocrine, Bone Diseases and Genetics Unit, Reference Centre for Rare Diseases of Calcium and Phosphate Metabolism, ERN BOND, OSCAR Network, Paediatric Research Unit, Children's Hospital, University Hospital; Infinity Center, Inserm CNRS UMR1291, University of Toulouse 3 Paul Sabatier, Toulouse, France.
Saber AmriInfinity Center, Inserm CNRS UMR1291, University of Toulouse 3 Paul Sabatier, Toulouse, France.
Mélissa GalindoInfinity Center, Inserm CNRS UMR1291, University of Toulouse 3 Paul Sabatier, Toulouse, France.
Emmanuelle LacassagneInfinity Center, Inserm CNRS UMR1291, University of Toulouse 3 Paul Sabatier, Toulouse, France.
Simon GeorgeMGX-Montpellier GenomiX, Univ. Montpellier, CNRS, Inserm, Montpellier, France.
Xavier MialheMGX-Montpellier GenomiX, Univ. Montpellier, CNRS, Inserm, Montpellier, France.
Émeline LhuillierI2MC - Institut des Maladies Métaboliques et Cardiovasculaires, Inserm, University of Toulouse 3 Paul Sabatier; GeT-Santé, Plateforme Génome et Transcriptome, GenoToul, Toulouse, France.
Nicolas FranchittoService d'Addictologie Clinique, Urgences Réanimation Médecine, CHU de Toulouse, Toulouse, France.
Freddy JeanneteauInstitut de Genomique Fonctionnelle, University of Montpellier, Inserm, CNRS, Montpellier, 34090, France.ORCID 0000-0002-9606-2892
Isabelle GenneroInfinity Center, Inserm CNRS UMR1291, University of Toulouse 3 Paul Sabatier; Laboratoire de Biochimie - Biologie moléculaire IFB Center CHU Toulouse, Toulouse, France.
Jean-Pierre SallesEndocrine, Bone Diseases and Genetics Unit, Reference Centre for Rare Diseases of Calcium and Phosphate Metabolism, ERN BOND, OSCAR Network, Paediatric Research Unit, Children's Hospital, University Hospital; Infinity Center, Inserm CNRS UMR1291, University of Toulouse 3 Paul Sabatier, Toulouse, France.ORCID 0000-0002-0941-8951
Maithé TauberCentre de Référence National du Syndrome de Prader-Willi et Syndromes avec Troubles du Comportement Alimentaire, Unité d'Endocrinologie, Hôpital des Enfants, Institut des Handicaps Neurologiques, Psychiatriques et Sensoriels, CHU de Toulouse; Infinity Center, Inserm CNRS UMR1291, University of Toulouse 3 Paul Sabatier, Toulouse, France.ORCID 0000-0002-0363-7862
Centre National de la Recherche Scientifique · FRCentre Hospitalier Universitaire de Toulouse · FRUniversité Toulouse III - Paul Sabatier · FR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionA microdeletion including the SNORD116 gene (SNORD116 MD) has been shown to drive the Prader-Willi syndrome (PWS) features. PWS is a neurodevelopmental disorder clinically characterized by endocrine impairment, intellectual disability and psychiatric symptoms such as a lack of emotional regulation, impulsivity, and intense temper tantrums with outbursts. In addition, this syndrome is associated with a nutritional trajectory characterized by addiction-like behavior around food in adulthood. PWS is related to the genetic loss of expression of a minimal region that plays a potential role in epigenetic regulation. Nevertheless, the role of the SNORD116 MD in DNA methylation, as well as the impact of the oxytocin (OXT) on it, have never been investigated in human neurons.

methodsWe studied the methylation marks in induced pluripotent stem-derived dopaminergic neurons carrying a SNORD116 MD in comparison with those from an age-matched adult healthy control. We also performed identical neuron differentiation in the presence of OXT. We performed a genome-wide DNA methylation analysis from the iPSC-derived dopaminergic neurons by reduced-representation bisulfite sequencing. In addition, we performed RNA sequencing analysis in these iPSC-derived dopaminergic neurons differentiated with or without OXT.

resultsThe analysis revealed that 153,826 cytosines were differentially methylated between SNORD116 MD neurons and control neurons. Among the differentially methylated genes, we determined a list of genes also differentially expressed. Enrichment analysis of this list encompassed the dopaminergic system with COMT and SLC6A3. COMT displayed hypermethylation and under-expression in SNORD116 MD, and SLC6A3 displayed hypomethylation and over-expression in SNORD116 MD. RT-qPCR confirmed significant over-expression of SLC6A3 in SNORD116 MD neurons. Moreover, the expression of this gene was significantly decreased in the case of OXT adjunction during the differentiation.

conclusionSNORD116 MD dopaminergic neurons displayed differential methylation and expression in the COMT and SLC6A3 genes, which are related to dopaminergic clearance.

Indexed as

Behavior, AddictiveDNA MethylationDopaminergic NeuronsInduced Pluripotent Stem CellsPrader-Willi SyndromeRNA, Small NucleolarAdultCell DifferentiationDopamine Plasma Membrane Transport ProteinsEpigenesis, GeneticFemaleHumansMaleOxytocinDopamine Plasma Membrane Transport ProteinsOxytocinRNA, Small NucleolarSNORD116 RNA, human

Identifiers

PMID38561465
OpenAlexW4393469814

What Socratic holds

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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 Socratic graph.