ArticleProceedings of the National Academy of Sciences of the United States of America2012
Purinergic signaling in human pluripotent stem cells is regulated by the housekeeping gene encoding hypoxanthine guanine phosphoribosyltransferase.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 52 citations in OpenAlex.
- From metabolic intermediary to neurotransmitter: purinergic signaling in neurophysiology and vulnerability of brain circuits.Bioscience reports · 2026Review
- Microcephaly-associated protein WDR62 supports purine metabolism by interacting with co-chaperone BAG2.The EMBO journal · 2026Article
- The precision strategy of human genome correction via a set of circular donor DNA and its cleaver.Frontiers in genome editing · 2026Article
- One-Carbon Metabolism and Midbrain Dopaminergic Cells in Lesch-Nyhan Disease.Molecular syndromology · 2025Review
- The Role of Purine Metabolism and Uric Acid in Postnatal Neurologic Development.Molecules (Basel, Switzerland) · 2025Review
- Unleashing the Power of Induced Pluripotent stem Cells in in vitro Modelling of Lesch-Nyhan Disease.Stem cell reviews and reports · 2025Review
- Dissecting genetic architecture of rare dystonia: genetic, molecular and clinical insights.Journal of medical genetics · 2024Article
- Purinergic Signaling and its Role in the Stem Cell Differentiation.Mini reviews in medicinal chemistry · 2024Review
- Inborn Errors of Purine Salvage and Catabolism.Metabolites · 2023Review
- Caveolin-1 Expression in the Dorsal Striatum Drives Methamphetamine Addiction-Like Behavior.International journal of molecular sciences · 2021Article
- Induced pluripotent stem cells from subjects with Lesch-Nyhan disease.Scientific reports · 2021Article
- PRPS1-mediated purine biosynthesis is critical for pluripotent stem cell survival and stemness.Aging · 2021Article
- In vivo reduction of striatal D1R by RNA interference alters expression of D1R signaling-related proteins and enhances methamphetamine addiction in male rats.Brain structure & function · 2020Article
- Formate metabolism in health and disease.Molecular metabolism · 2020Review
- Animal Model Contributions to Congenital Metabolic Disease.Advances in experimental medicine and biology · 2020Review
- Organs to Cells and Cells to Organoids: The Evolution ofFrontiers in cellular neuroscience · 2019Review
- Emerging Role of Purine Metabolizing Enzymes in Brain Function and Tumors.International journal of molecular sciences · 2018Review
- Purinergic Receptor Expression and Potential Association with Human Embryonic Stem Cell-Derived Oligodendrocyte Progenitor Cell Development.Cell journal · 2017Article
- The hypothesis that Helicobacter pylori predisposes to Alzheimer's disease is biologically plausible.Scientific reports · 2017Article
- Utility of Induced Pluripotent Stem Cells for the Study and Treatment of Genetic Diseases: Focus on Childhood Neurological Disorders.Frontiers in molecular neuroscience · 2016Review
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Lesch-Nyhan disease (LND) is an X-linked genetic disorder caused by mutations of the hypoxanthine guanine phosphoribosyltransferase (HPRT) purine biosynthesis gene and characterized by aberrant purine metabolism, deficient basal ganglia dopamine levels, dystonia, and severe neurobehavioral manifestations, including compulsive self-injurious behavior. Although available evidence has identified important roles for purinergic signaling in brain development, the mechanisms linking HPRT deficiency, purinergic pathways, and neural dysfunction of LND are poorly understood. In these studies aimed at characterizing purinergic signaling in HPRT deficiency, we used a lentivirus vector stably expressing an shRNA targeted to the HPRT gene to produce HPRT-deficient human CVB induced pluripotent stem cells and human HUES11 embryonic stem cells. Both CVB and HUES11 cells show >99% HPRT knockdown and demonstrate markedly decreased expression of the purinergic P2Y1 receptor mRNA. In CVB cells, P2Y1 mRNA and protein down-regulation by HPRT knockdown is refractory to activation by the P2Y1 receptor agonist ATP and shows aberrant purinergic signaling, as reflected by marked deficiency of the transcription factor pCREB and constitutive activation of the MAP kinases phospho-ERK1/2. Moreover, HPRT-knockdown CVB cells also demonstrate marked reduction of phosphorylated β-catenin. These results indicate that the housekeeping gene HPRT regulates purinergic signaling in pluripotent human stem cells, and that this regulation occurs at least partly through aberrant P2Y1-mediated expression and signaling. We propose that such mechanisms may play a role in the neuropathology of HPRT-deficiency LND and may point to potential molecular targets for modulation of this intractable neurological phenotype.
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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 OpenQuestion graph.