Evidence map›Paper›PMID 34214487›Full record

ArticleStem cell reports2021

Lesch-Nyhan disease causes impaired energy metabolism and reduced developmental potential in midbrain dopaminergic cells.

Scott Bell, Vincent McCarty, Huashan Peng, Malvin Jefri, Nuwan Hettige, Lilit Antonyan, Liam Crapper, Liam A O'Leary, Xin Zhang, Ying Zhang and 15 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Stem cell reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
2.8field-weighted citation impact, top 8% 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

20 citing papers in PubMed, 47 citations in OpenAlex.

  1. A new conditional mouse model for Cre-mediated restoration ofbioRxiv : the preprint server for biology · 2026
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  13. The Contribution of Type 2 Diabetes to Parkinson's Disease Aetiology.International journal of molecular sciences · 2024
    Review
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  15. Review
  16. Transcriptional Dysregulation and Impaired Neuronal Activity inInternational journal of molecular sciences · 2023
    Article
  17. Review
  18. Review
  19. 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

25 authors at 6 institutions in 3 countries.

Scott BellPsychiatric Genetics Group, McGill University, Montreal, QC, Canada; Department of Psychiatry, McGill University and Douglas Hospital Research Institute, 6875 LaSalle Boulevard, Frank Common Building, Room 2101.2, Montreal, QC H4H 1R3, Canada.
Vincent McCartyPsychiatric Genetics Group, McGill University, Montreal, QC, Canada; Department of Psychiatry, McGill University and Douglas Hospital Research Institute, 6875 LaSalle Boulevard, Frank Common Building, Room 2101.2, Montreal, QC H4H 1R3, Canada.
Huashan PengPsychiatric Genetics Group, McGill University, Montreal, QC, Canada; Department of Psychiatry, McGill University and Douglas Hospital Research Institute, 6875 LaSalle Boulevard, Frank Common Building, Room 2101.2, Montreal, QC H4H 1R3, Canada.
Malvin JefriPsychiatric Genetics Group, McGill University, Montreal, QC, Canada; Department of Psychiatry, McGill University and Douglas Hospital Research Institute, 6875 LaSalle Boulevard, Frank Common Building, Room 2101.2, Montreal, QC H4H 1R3, Canada.
Nuwan HettigePsychiatric Genetics Group, McGill University, Montreal, QC, Canada; Department of Psychiatry, McGill University and Douglas Hospital Research Institute, 6875 LaSalle Boulevard, Frank Common Building, Room 2101.2, Montreal, QC H4H 1R3, Canada.
Lilit AntonyanPsychiatric Genetics Group, McGill University, Montreal, QC, Canada; Department of Psychiatry, McGill University and Douglas Hospital Research Institute, 6875 LaSalle Boulevard, Frank Common Building, Room 2101.2, Montreal, QC H4H 1R3, Canada.
Liam CrapperPsychiatric Genetics Group, McGill University, Montreal, QC, Canada; Department of Psychiatry, McGill University and Douglas Hospital Research Institute, 6875 LaSalle Boulevard, Frank Common Building, Room 2101.2, Montreal, QC H4H 1R3, Canada.
Liam A O'LearyPsychiatric Genetics Group, McGill University, Montreal, QC, Canada; Department of Psychiatry, McGill University and Douglas Hospital Research Institute, 6875 LaSalle Boulevard, Frank Common Building, Room 2101.2, Montreal, QC H4H 1R3, Canada.
Xin ZhangPsychiatric Genetics Group, McGill University, Montreal, QC, Canada; Department of Psychiatry, McGill University and Douglas Hospital Research Institute, 6875 LaSalle Boulevard, Frank Common Building, Room 2101.2, Montreal, QC H4H 1R3, Canada.
Ying ZhangPsychiatric Genetics Group, McGill University, Montreal, QC, Canada; Department of Psychiatry, McGill University and Douglas Hospital Research Institute, 6875 LaSalle Boulevard, Frank Common Building, Room 2101.2, Montreal, QC H4H 1R3, Canada.
Hanrong WuPsychiatric Genetics Group, McGill University, Montreal, QC, Canada; Department of Psychiatry, McGill University and Douglas Hospital Research Institute, 6875 LaSalle Boulevard, Frank Common Building, Room 2101.2, Montreal, QC H4H 1R3, Canada.
Diane SutcliffeDepartment of Neurology, Emory University, Atlanta, GA, USA; Department of Human Genetics, Emory University, Atlanta, GA, USA; Department of Pediatrics, Emory University, Atlanta, GA, USA.
Ilaria KolobovaPsychiatric Genetics Group, McGill University, Montreal, QC, Canada; Department of Psychiatry, McGill University and Douglas Hospital Research Institute, 6875 LaSalle Boulevard, Frank Common Building, Room 2101.2, Montreal, QC H4H 1R3, Canada.
Thad A RosenbergerDepartment of Pharmacology, Physiology, and Therapeutics, School of Medicine and Health Sciences, University of North Dakota, Grand Forks, ND, USA.
Luc MoquinDepartment of Psychiatry, McGill University and Douglas Hospital Research Institute, 6875 LaSalle Boulevard, Frank Common Building, Room 2101.2, Montreal, QC H4H 1R3, Canada.
Alain GrattonDepartment of Psychiatry, McGill University and Douglas Hospital Research Institute, 6875 LaSalle Boulevard, Frank Common Building, Room 2101.2, Montreal, QC H4H 1R3, Canada.
Jelena PopicDepartment of Biochemistry, McGill University, Montreal, QC, Canada; Rosalind and Morris Goodman Cancer Research Centre, McGill University, Montreal, QC, Canada.
Ilse GantoisDepartment of Biochemistry, McGill University, Montreal, QC, Canada; Rosalind and Morris Goodman Cancer Research Centre, McGill University, Montreal, QC, Canada.
Patrick S StumpfJoint Research Center for Computational Biomedicine, RWTH Aachen University, Aachen, Germany.
Andreas A SchuppertJoint Research Center for Computational Biomedicine, RWTH Aachen University, Aachen, Germany.
Naguib MechawarDepartment of Psychiatry, McGill University and Douglas Hospital Research Institute, 6875 LaSalle Boulevard, Frank Common Building, Room 2101.2, Montreal, QC H4H 1R3, Canada.
Nahum SonenbergDepartment of Biochemistry, McGill University, Montreal, QC, Canada; Rosalind and Morris Goodman Cancer Research Centre, McGill University, Montreal, QC, Canada.
Michel L TremblayDepartment of Biochemistry, McGill University, Montreal, QC, Canada; Rosalind and Morris Goodman Cancer Research Centre, McGill University, Montreal, QC, Canada.
Hyder A JinnahDepartment of Neurology, Emory University, Atlanta, GA, USA; Department of Human Genetics, Emory University, Atlanta, GA, USA; Department of Pediatrics, Emory University, Atlanta, GA, USA.
Carl ErnstPsychiatric Genetics Group, McGill University, Montreal, QC, Canada; Department of Psychiatry, McGill University and Douglas Hospital Research Institute, 6875 LaSalle Boulevard, Frank Common Building, Room 2101.2, Montreal, QC H4H 1R3, Canada. Electronic address: carl.ernst@mcgill.ca.
McGill University · CADouglas Mental Health University Institute · CAEmory University · USRWTH Aachen University · DEMcGill University Health Centre · CAUniversity of North Dakota · US

Funding

Modeling Inherited Neurodevelopmental Disorders with Human Induced Pluripotent Stem CellsR01NS109242 · NINDS · EMORY UNIVERSITY · PI JINNAH, HYDER A · 2019 to 2022
$2.4M
Human Induced Pluripotent Stem Cells As Models for Inherited Developmental DisordersR56NS102980 · NINDS · EMORY UNIVERSITY · PI JINNAH, HYDER A · 2017 to 2017
$546k
CIHRNINDS NIH HHS R01 NS109242NINDS NIH HHS R56 NS102980
6 · The paper itself

Abstract

Mutations in HPRT1, a gene encoding a rate-limiting enzyme for purine salvage, cause Lesch-Nyhan disease which is characterized by self-injury and motor impairments. We leveraged stem cell and genetic engineering technologies to model the disease in isogenic and patient-derived forebrain and midbrain cell types. Dopaminergic progenitor cells deficient in HPRT showed decreased intensity of all developmental cell-fate markers measured. Metabolic analyses revealed significant loss of all purine derivatives, except hypoxanthine, and impaired glycolysis and oxidative phosphorylation. real-time glucose tracing demonstrated increased shunting to the pentose phosphate pathway for de novo purine synthesis at the expense of ATP production. Purine depletion in dopaminergic progenitor cells resulted in loss of RHEB, impairing mTORC1 activation. These data demonstrate dopaminergic-specific effects of purine salvage deficiency and unexpectedly reveal that dopaminergic progenitor cells are programmed to a high-energy state prior to higher energy demands of terminally differentiated cells.

Indexed as

Energy MetabolismBiomarkersCell LineageCerebral CortexDopaminergic NeuronsGlucoseGlycolysisHumansHypoxanthine PhosphoribosyltransferaseLesch-Nyhan SyndromeMechanistic Target of Rapamycin Complex 1MesencephalonNeural Stem CellsOxidative PhosphorylationPentose Phosphate PathwayPurinesBiomarkersGlucoseHypoxanthine PhosphoribosyltransferaseMechanistic Target of Rapamycin Complex 1PurinesdopamineiPSCLesch-Nyhan diseasemTORC1neurodevelopmentpurines

Identifiers

PMID34214487
PMCPMC8282463
OpenAlexW3175230945

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.