Evidence map›Paper›PMID 42349423›Full record

ArticleStem cell reports2026

Integrative analysis of drug-gene signatures in human pluripotent stem cells reveals prazosin as a novel SQSTM1 regulator for ALS therapeutics.

Florine Roussange, Jacqueline Gide, Johana Tournois, Michel Cailleret, Anne Boland, Christophe Battail, Jean-François Deleuze, Hélène Polvèche, Didier Auboeuf, Knut Brockmann and 9 more

Abstract read
In one paragraph

Article in Stem cell reports, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Article
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

19 authors.

Florine RoussangeUniversité Paris Saclay, Université d'Evry, Inserm, IStem, UMR861, 91100 Corbeil-Essonnes, France.
Jacqueline GideIStem, CECS, 91100 Corbeil-Essonnes, France.
Johana TournoisIStem, CECS, the research and innovation team, 91100 Corbeil-Essonnes, France.
Michel CailleretUniversité Paris Saclay, Université d'Evry, Inserm, IStem, UMR861, 91100 Corbeil-Essonnes, France.
Anne BolandUniversité Paris-Saclay, CEA, Centre National de Recherche en Génomique Humaine (CNRGH), 91057 Evry, France.
Christophe BattailUniversité Paris-Saclay, CEA, Centre National de Recherche en Génomique Humaine (CNRGH), 91057 Evry, France; Université Grenoble Alpes, Inserm, CEA, UA13, BGE, 38000 Grenoble, France.
Jean-François DeleuzeUniversité Paris-Saclay, CEA, Centre National de Recherche en Génomique Humaine (CNRGH), 91057 Evry, France.
Hélène PolvècheIStem, CECS, the research and innovation team, 91100 Corbeil-Essonnes, France.
Didier AuboeufEcole Normale Supérieure de Lyon, Inserm, U1293, CNRS, UMR 5239, Université Claude Bernard Lyon 1, Laboratory of Biology and Modelling of the Cell, 46 allée d'Italie 69364 Lyon, France.
Knut BrockmannDepartment of Pediatrics and Adolescent Medicine, University Medical Center, Göttingen, Germany.
Edor KabashiLaboratory of Translational Research for Neurological Disorders, Imagine Institute, Université de Paris, INSERM, UMR 1163, 75015 Paris, France.
Anca MarianLaboratory of Translational Research for Neurological Disorders, Imagine Institute, Université de Paris, INSERM, UMR 1163, 75015 Paris, France.
Lina El KassarIStem, CECS, the research and innovation team, 91100 Corbeil-Essonnes, France.
Sophie BlondelIStem, CECS, 91100 Corbeil-Essonnes, France.
François SalachasSorbonne Université, Institut du Cerveau - Paris Brain Institute - ICM, APHP, Inserm, CNRS, Département de Neurologie, Centre SLA de Paris, Hôpital Pitié-Salpêtrière, 75013 Paris, France.
Gaëlle BruneteauSorbonne Université, Institut du Cerveau - Paris Brain Institute - ICM, APHP, Inserm, CNRS, Département de Neurologie, Centre SLA de Paris, Hôpital Pitié-Salpêtrière, 75013 Paris, France; Alliance on Clinical Trials for ALS-MND (ACT4ALS-MND), Neuroscience Clinical Investigation Center, Paris Brain Institute, 75013 Paris, France.
Marc PeschanskiIStem, CECS, 91100 Corbeil-Essonnes, France.
Cécile MartinatUniversité Paris Saclay, Université d'Evry, Inserm, IStem, UMR861, 91100 Corbeil-Essonnes, France; IStem, CECS, 91100 Corbeil-Essonnes, France. Electronic address: cmartinat@istem.fr.
Sandrine BaghdoyanUniversité Paris Saclay, Université d'Evry, Inserm, IStem, UMR861, 91100 Corbeil-Essonnes, France.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The classical paradigm of drug screening often faces significant limitations due to the challenges associated with identifying molecular or cellular read-outs that are relevant to specific genetic diseases. To remedy this, an alternative approach of reverse phenotypic mapping was tested: Compounds were evaluated for their effects on gene expression and alternative splicing in a healthy cell model, and the resulting data were matched to molecular signatures of diseases. A subset of 50 drugs was tested on mesenchymal stem cells derived from a human pluripotent stem cell line. Over half of the compounds altered gene expression, many affecting pathways linked to monogenic diseases. One hit, increased SQSTM1 expression induced by prazosin, was further validated in FTD/ALS type 3 models caused by SQSTM1 haploinsufficiency, including patient-derived fibroblasts, SQSTM1-depleted hiPSC-derived motor neurons, and a zebrafish model. Extending this paradigm could involve testing diverse cell types and larger drug libraries.

Indexed as

Amyotrophic Lateral SclerosisPluripotent Stem CellsSequestosome-1 ProteinAnimalsCell LineFibroblastsGene Expression ProfilingGene Expression RegulationHumansInduced Pluripotent Stem CellsMotor NeuronsZebrafishSequestosome-1 ProteinSQSTM1 protein, humanamyotrophic lateral sclerosisautophagydrug repositioninggene expression mappingmotor neuronspersonalized therapiespluripotent stem cellsrepurposingSQSTM1

Identifiers

PMID42349423
PMCPMC13385447

What Socratic 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 Socratic graph.