Evidence map›Paper›PMID 38773714›Full record

ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2024

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.

Swagata Ghatak, Jolene K Diedrich, Maria Talantova, Nivedita Bhadra, Henry Scott, Meetal Sharma, Matthew Albertolle, Nicholas J Schork, John R Yates, Stuart A Lipton

Abstract read
In one paragraph

Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing 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

15 citing papers in PubMed.

  1. Article
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  5. Article
  6. Subcellular mass spectrometry reveals proteome remodeling in an asymmetrically dividing (frog) embryonic stem cell.Proceedings of the National Academy of Sciences of the United States of America · 2026
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  9. 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

10 authors.

Swagata GhatakNeurodegeneration New Medicines Center, The Scripps Research Institute, La Jolla, CA, 92037, USA.
Jolene K DiedrichDepartment of Molecular Medicine, The Scripps Research Institute, La Jolla, CA, 92037, USA.
Maria TalantovaNeurodegeneration New Medicines Center, The Scripps Research Institute, La Jolla, CA, 92037, USA.
Nivedita BhadraQuantitative Medicine and Systems Biology, The Translational Genomics Research Institute, Phoenix, AZ, 85004, USA.
Henry ScottNeurodegeneration New Medicines Center, The Scripps Research Institute, La Jolla, CA, 92037, USA.
Meetal SharmaNeurodegeneration New Medicines Center, The Scripps Research Institute, La Jolla, CA, 92037, USA.
Matthew AlbertolleNeurodegeneration New Medicines Center, The Scripps Research Institute, La Jolla, CA, 92037, USA.
Nicholas J SchorkQuantitative Medicine and Systems Biology, The Translational Genomics Research Institute, Phoenix, AZ, 85004, USA.
John R YatesDepartment of Molecular Medicine, The Scripps Research Institute, La Jolla, CA, 92037, USA.
Stuart A LiptonNeurodegeneration New Medicines Center, The Scripps Research Institute, La Jolla, CA, 92037, USA.ORCID 0000-0002-3490-1259

Funding

Systems BiologyU19AG023122 · NIA · TRANSLATIONAL GENOMICS RESEARCH INST · PI RICHARD A MILLER · 2004 to 2026
$102.6M
Regulatory and Human Study Operations (RHSO) Core CU19AG065169 · NIA · UNIVERSITY OF ARIZONA · PI HUENTELMAN, MATT · 2021 to 2025
$59.8M
Exceptional Longevity Data Management and Coordinating CenterU24AG078753 · NIA · SAGE BIONETWORKS · PI Christine M. Fabre Suver, Solveig Sieberts · 2022 to 2026
$10.3M
Proteogenetics of Autism Spectrum DisordersR01MH100175 · NIMH · SCRIPPS RESEARCH INSTITUTE, THE · PI MUOTRI, ALYSSON R., YATES III, JOHN R · 2013 to 2025
$7.4M
Novel Proteomics Approach to HIV-Associated Neurocognitive Disorder & Drug AbuseDP1DA041722 · NIDA · SCRIPPS RESEARCH INSTITUTE, THE · PI LIPTON, STUART A · 2016 to 2020
$7.0M
Leadership in AD/ADRD Drug DiscoveryR35AG071734 · NIA · SCRIPPS RESEARCH INSTITUTE, THE · PI LIPTON, STUART A · 2021 to 2025
$5.4M
Omics Analyses of HIV and Substance Use DisorderR01DA048882 · NIDA · SCRIPPS RESEARCH INSTITUTE, THE · PI REPUNTE-CANONIGO, VEZ · 2019 to 2023
$4.3M
Dynamic Interactions of the S-Nitrosoproteome in Type 2 Diabetes/Metabolic Syndrome and Alzheimer’s DiseaseRF1AG057409 · NIA · SCRIPPS RESEARCH INSTITUTE, THE · PI LIPTON, STUART A · 2017 to 2020
$4.1M
S-Nitrosylation-Induced Posttranslational Modification and Aberrant Cell Signaling in Sporadic Alzheimer's DiseaseR01AG056259 · NIA · SCRIPPS RESEARCH INSTITUTE, THE · PI LIPTON, STUART A · 2017 to 2021
$3.3M
Integrative Omics to enhance therapeutics development for healthy agingUH3AG064706 · NIA · TRANSLATIONAL GENOMICS RESEARCH INST · PI MILLER, RICHARD A, SCHORK, NICHOLAS JOSEPH · 2021 to 2024
$3.3M
Aberrant protein S-nitrosylation mediates Gene-Environment Interactions in AD/ADRDU01AG088679 · NIA · SCRIPPS RESEARCH INSTITUTE, THE · PI STUART A LIPTON, Tomohiro Nakamura · 2024 to 2026
$2.7M
Pro-Electrophilic Drugs PEDs for Alzheimer's DiseaseR56AG065372 · NIA · SCRIPPS RESEARCH INSTITUTE, THE · PI LIPTON, STUART A · 2020 to 2021
$1.8M
NIA NIH HHS R01 AG056259NIA NIH HHS R35 AG071734NIA NIH HHS R56 AG065372NIA NIH HHS RF1 AG057409NIA NIH HHS U01 AG088679NIA NIH HHS U19 AG023122NIA NIH HHS U19 AG065169NIA NIH HHS U24 AG078753NIA NIH HHS UH3 AG064706NIDA NIH HHS DP1 DA041722NIDA NIH HHS R01 DA048882NIEHS NIH HHS F32 ES031815NIH HHS DP1DA041722NIH HHS F32ES031815NIH HHS R01AG056259NIH HHS R01DA048882NIH HHS R01MH100175NIH HHS R21MH129776NIH HHS R35AG071734NIH HHS R56AG065372NIH HHS RF1AG057409NIH HHS U19AG023122NIH HHS U19AG065169NIH HHS U24AG078753NIH HHS UH3AG064706NIMH NIH HHS R01 MH100175NIMH NIH HHS R21 MH129776
6 · The paper itself

Abstract

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.

Indexed as

Alzheimer DiseaseInduced Pluripotent Stem CellsNeuronsPatch-Clamp TechniquesProteomicsHumansSingle-Cell AnalysisAlzheimer's diseasehiPSC‐derived neuronspatch clamp electrophysiology, single‐cell proteomics

Identifiers

PMID38773714
PMCPMC11304297

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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 OpenQuestion graph.