دورية أكاديمية
Single-Cell Patch-Clamp/Proteomics of Human Alzheimer's Disease iPSC-Derived Excitatory Neurons Versus Isogenic Wild-Type Controls Suggests Novel Causation and Therapeutic Targets.
العنوان: | Single-Cell Patch-Clamp/Proteomics of Human Alzheimer's Disease iPSC-Derived Excitatory Neurons Versus Isogenic Wild-Type Controls Suggests Novel Causation and Therapeutic Targets. |
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المؤلفون: | Ghatak S; Neurodegeneration New Medicines Center, The Scripps Research Institute, La Jolla, CA, 92037, USA.; Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA, 92037, USA., Diedrich JK; Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA, 92037, USA., Talantova M; Neurodegeneration New Medicines Center, The Scripps Research Institute, La Jolla, CA, 92037, USA.; Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA, 92037, USA., Bhadra N; Quantitative Medicine and Systems Biology, The Translational Genomics Research Institute, Phoenix, AZ, 85004, USA., Scott H; Neurodegeneration New Medicines Center, The Scripps Research Institute, La Jolla, CA, 92037, USA.; Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA, 92037, USA., Sharma M; Neurodegeneration New Medicines Center, The Scripps Research Institute, La Jolla, CA, 92037, USA.; Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA, 92037, USA., Albertolle M; Neurodegeneration New Medicines Center, The Scripps Research Institute, La Jolla, CA, 92037, USA.; Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA, 92037, USA., Schork NJ; Quantitative Medicine and Systems Biology, The Translational Genomics Research Institute, Phoenix, AZ, 85004, USA., Yates JR 3rd; Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA, 92037, USA., Lipton SA; Neurodegeneration New Medicines Center, The Scripps Research Institute, La Jolla, CA, 92037, USA.; Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA, 92037, USA.; Department of Neurosciences, School of Medicine, University of California, San Diego, La Jolla, CA, 92093, USA. |
المصدر: | Advanced science (Weinheim, Baden-Wurttemberg, Germany) [Adv Sci (Weinh)] 2024 Aug; Vol. 11 (29), pp. e2400545. Date of Electronic Publication: 2024 May 21. |
نوع المنشور: | Journal Article |
اللغة: | English |
بيانات الدورية: | Publisher: WILEY-VCH Country of Publication: Germany NLM ID: 101664569 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2198-3844 (Electronic) Linking ISSN: 21983844 NLM ISO Abbreviation: Adv Sci (Weinh) Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: Weinheim : WILEY-VCH, [2014]- |
مواضيع طبية MeSH: | Alzheimer Disease*/metabolism , Alzheimer Disease*/genetics , Induced Pluripotent Stem Cells*/metabolism , Proteomics*/methods , Neurons*/metabolism , Patch-Clamp Techniques*/methods, Humans ; Single-Cell Analysis/methods |
مستخلص: | Standard single-cell (sc) proteomics of disease states inferred from multicellular organs or organoids cannot currently be related to single-cell physiology. Here, a scPatch-Clamp/Proteomics platform is developed on single neurons generated from hiPSCs bearing an Alzheimer's disease (AD) genetic mutation and compares them to isogenic wild-type controls. This approach provides both current and voltage electrophysiological data plus detailed proteomics information on single-cells. With this new method, the authors are able to observe hyperelectrical activity in the AD hiPSC-neurons, similar to that observed in the human AD brain, and correlate it to ≈1400 proteins detected at the single neuron level. Using linear regression and mediation analyses to explore the relationship between the abundance of individual proteins and the neuron's mutational and electrophysiological status, this approach yields new information on therapeutic targets in excitatory neurons not attainable by traditional methods. This combined patch-proteomics technique creates a new proteogenetic-therapeutic strategy to correlate genotypic alterations to physiology with protein expression in single-cells. (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.) |
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معلومات مُعتمدة: | DP1DA041722 United States NH NIH HHS; R56 AG065372 United States AG NIA NIH HHS; F32ES031815 United States NH NIH HHS; R01 MH100175 United States MH NIMH NIH HHS; UH3 AG064706 United States AG NIA NIH HHS; F32 ES031815 United States ES NIEHS NIH HHS; DP1 DA041722 United States DA NIDA NIH HHS; R21 MH129776 United States MH NIMH NIH HHS; R21MH129776 United States NH NIH HHS; U19AG023122 United States NH NIH HHS; R35AG071734 United States NH NIH HHS; R01MH100175 United States NH NIH HHS; U24 AG078753 United States AG NIA NIH HHS; UH3AG064706 United States NH NIH HHS; R56AG065372 United States NH NIH HHS; R35 AG071734 United States AG NIA NIH HHS; U19 AG023122 United States AG NIA NIH HHS; R01 AG056259 United States AG NIA NIH HHS; U19AG065169 United States NH NIH HHS; R01 DA048882 United States DA NIDA NIH HHS; R01DA048882 United States NH NIH HHS; RF1 AG057409 United States AG NIA NIH HHS; U19 AG065169 United States AG NIA NIH HHS; U24AG078753 United States NH NIH HHS; RF1AG057409 United States NH NIH HHS; R01AG056259 United States NH NIH HHS |
فهرسة مساهمة: | Keywords: Alzheimer's disease; hiPSC‐derived neurons; patch clamp electrophysiology, single‐cell proteomics |
تواريخ الأحداث: | Date Created: 20240522 Date Completed: 20240807 Latest Revision: 20240809 |
رمز التحديث: | 20240809 |
مُعرف محوري في PubMed: | PMC11304297 |
DOI: | 10.1002/advs.202400545 |
PMID: | 38773714 |
قاعدة البيانات: | MEDLINE |
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