ArticleCell2024
Human iPSC 4R tauopathy model uncovers modifiers of tau propagation.
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Article in Cell, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers, 1 of them a synthesis that pooled it.
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61citing papers in PubMed, 1 pooled it
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Who cites it
61 citing papers in PubMed, 1 synthesis or guideline pooled it, 60 citations in OpenAlex.
- Human induced pluripotent stem cell models for Alzheimer's disease research: a bibliometric analysis.Frontiers in human neuroscience · 2025Pooled it
- Article
- Modeling human neurodegeneration with iPSCs: opportunities, limitations, and the challenge of aging.The Journal of clinical investigation · 2026Review
- CRISPR-associated enzymes are mislocalized to the cytoplasm in iPSC-derived neurons, resulting in KRAB(KOX1)-specific degradation.Cell systems · 2026Article
- Discovery and Characterization of Inhibitors of Ubiquitin-Like Modifier Activating Enzyme 5 (UBA5): Targeting the UFMylation Pathway in Cancer and Neurodegenerative Diseases.ACS chemical biology · 2026Article
- Human iPSC models revealResearch square · 2026Article
- cGAS-mediated type I IFN signaling contributes to disease progression in drug-refractory epilepsy.Nature neuroscience · 2026Article
- Scalable human neuronal models of tauopathy producing endogenous seed-competent 4R tau.Science advances · 2026Article
- Limited Detectability of Network Functional Alterations in a Tauopathy Model Using Mouse Primary Cortical Cultures.Biomedicines · 2026Article
- SORLA up-regulation suppresses pathological effects in aged tauopathy mouse brain.Science advances · 2026Article
- Patient-derived tau-seeded human neuronal chimeras recapitulate mature Alzheimer's tau pathology and uncover human-specific neuronal vulnerability.bioRxiv : the preprint server for biology · 2026Article
- Recent advances in Alzheimer's disease: From molecular mechanisms to therapeutic strategies.Cell · 2026Review
- Reducing PI4KIIIα Levels or Activity Limits Tau Seed Internalization and Assembly in Human Cortical Neurons.Cells · 2026Article
- A metabolite extracted from Escherichia coli suppresses tau aggregation.The Biochemical journal · 2026Article
- The mechanistic basis and cellular functions of UFMylation.Nature reviews. Molecular cell biology · 2026Review
- Single-nucleus epigenomic dysregulation unmasks genetic risk-associated neurodegenerative glia states.Nature communications · 2026Article
- Autophagy-Neuroinflammation Axis in Neurodegenerative Diseases: Mechanisms and Therapeutic Potential.Cells · 2026Review
- Genome-Wide CRISPR Screening Identifies Genetic Modulators of Amyloid Precursor Protein Processing.International journal of molecular sciences · 2026Article
- CRISPR tiling deletion screens reveal functional enhancers and allelic compensation effects (ACE) on SIN3A transcription.Nature communications · 2026Article
- Interactome mapping in human excitatory neurons reveals novel risk genes and pathways in Alzheimer's disease.bioRxiv : the preprint server for biology · 2026Article
1 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
29 authors at 6 institutions in 3 countries.
Celeste Parra BravoHelen and Robert Appel Alzheimer's Disease Institute, Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY 10021, USA; Neuroscience Graduate Program, Weill Cornell Medicine, New York, NY 10021, USA.
Alice Maria GianiHelen and Robert Appel Alzheimer's Disease Institute, Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY 10021, USA.
Jesus Madero-PerezHelen and Robert Appel Alzheimer's Disease Institute, Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY 10021, USA.
Zeping ZhaoHelen and Robert Appel Alzheimer's Disease Institute, Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY 10021, USA.
Yuansong WanHelen and Robert Appel Alzheimer's Disease Institute, Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY 10021, USA.
Avi J SamelsonInstitute for Neurodegenerative Diseases, Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94143, USA.
Man Ying WongHelen and Robert Appel Alzheimer's Disease Institute, Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY 10021, USA.
Alessandro EvangelistiHelen and Robert Appel Alzheimer's Disease Institute, Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY 10021, USA.
Ethan CordesHelen and Robert Appel Alzheimer's Disease Institute, Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY 10021, USA.
Li FanHelen and Robert Appel Alzheimer's Disease Institute, Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY 10021, USA.
Pearly YeHelen and Robert Appel Alzheimer's Disease Institute, Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY 10021, USA.
Daphne ZhuHelen and Robert Appel Alzheimer's Disease Institute, Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY 10021, USA.
Tatyana PoznerHelen and Robert Appel Alzheimer's Disease Institute, Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY 10021, USA.
Maria MercedesHelen and Robert Appel Alzheimer's Disease Institute, Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY 10021, USA.
Tark PatelDepartment of Biochemistry, University of Alberta, Edmonton, AB T6G 2H7, Canada.
Allan YarahmadyDepartment of Biochemistry, University of Alberta, Edmonton, AB T6G 2H7, Canada.
Gillian K CarlingHelen and Robert Appel Alzheimer's Disease Institute, Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY 10021, USA.
Fredrik H SterkyDepartment of Laboratory Medicine, University of Gothenburg, 41345 Gothenburg, Sweden; Department of Clinical Chemistry, Sahlgrenska University Hospital, 41345 Gothenburg, Sweden.
Virginia M Y LeeCenter for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
Edward B LeeInstitute of Aging, Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
Michael DeTureDepartment of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USA.
Dennis W DicksonDepartment of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USA.
Manu SharmaHelen and Robert Appel Alzheimer's Disease Institute, Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY 10021, USA.
Sue-Ann MokDepartment of Biochemistry, University of Alberta, Edmonton, AB T6G 2H7, Canada.
Wenjie LuoHelen and Robert Appel Alzheimer's Disease Institute, Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY 10021, USA.
Mingrui ZhaoHelen and Robert Appel Alzheimer's Disease Institute, Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY 10021, USA.
Martin KampmannInstitute for Neurodegenerative Diseases, Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94143, USA.
Shiaoching GongHelen and Robert Appel Alzheimer's Disease Institute, Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY 10021, USA. Electronic address: shg3006@med.cornell.edu.
Li GanHelen and Robert Appel Alzheimer's Disease Institute, Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY 10021, USA; Neuroscience Graduate Program, Weill Cornell Medicine, New York, NY 10021, USA. Electronic address: lig2033@med.cornell.edu.
Cornell University · USUniversity of Alberta · CAMayo Clinic in Florida · USUniversity of California, San Francisco · USUniversity of Pennsylvania · USSahlgrenska University Hospital · SE
Funding
Research Education ComponentP30AG072979 · NIA · UNIVERSITY OF PENNSYLVANIA · PI DAVID A WOLK · 2021 to 2026
$24.8MProject 3: Autophagy dysfunction and neuronal activity in FTDU54NS100717 · NINDS · WEILL MEDICAL COLL OF CORNELL UNIV · PI CUERVO, ANA MARIA · 2016 to 2020
$10.8MElucidate the roles of Alzheimer's disease risk genes and variants in gene expression and AD-related phenotypesRF1AG079557 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI GAN, LI, SHEN, YIN · 2022 to 2025
$6.1MStudy of Selective Cell and System Vulnerability in Alzheimer's DiseaseR01AG079291 · NIA · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Li Gan, Yun Li · 2023 to 2026
$5.4McGAS inhibitors for Alzheimer's disease treatmentR01AG074541 · NIA · WEILL MEDICAL COLL OF CORNELL UNIV · PI GAN, LI, SINHA, SUBHASH C · 2021 to 2025
$4.2MMaladaptive antiviral pathways in Alzheimer's diseaseR01AG072758 · NIA · WEILL MEDICAL COLL OF CORNELL UNIV · PI GAN, LI · 2021 to 2025
$4.1MTau acetylation in Alzheimer's diseaseR01AG054214 · NIA · WEILL MEDICAL COLL OF CORNELL UNIV · PI GAN, LI · 2017 to 2021
$3.3MPathogenesis of TauopathiesR01AG076434 · NIA · UNIVERSITY OF PENNSYLVANIA · PI VIRGINIA M LEE · 2023 to 2026
$3.0MWeill Cornell Initiative for Maximizing Student DevelopmentR25GM130494 · NIGMS · WEILL MEDICAL COLL OF CORNELL UNIV · PI CARRASCO, YAZMIN PAULINA, CESARMAN, ETHEL · 2019 to 2023
$2.4MEssential roles of DAP12 in tau metabolism and inflammation in Alzheimer's diseaseR01AG064239 · NIA · WEILL MEDICAL COLL OF CORNELL UNIV · PI LUO, WENJIE · 2020 to 2024
$2.1MNIA NIH HHS P30 AG072979NIA NIH HHS R01 AG054214NIA NIH HHS R01 AG064239NIA NIH HHS R01 AG072758NIA NIH HHS R01 AG074541NIA NIH HHS R01 AG076434NIA NIH HHS R01 AG079291NIA NIH HHS RF1 AG079557NIGMS NIH HHS R25 GM130494NINDS NIH HHS U54 NS100717
Abstract
Tauopathies are age-associated neurodegenerative diseases whose mechanistic underpinnings remain elusive, partially due to a lack of appropriate human models. Here, we engineered human induced pluripotent stem cell (hiPSC)-derived neuronal lines to express 4R Tau and 4R Tau carrying the P301S MAPT mutation when differentiated into neurons. 4R-P301S neurons display progressive Tau inclusions upon seeding with Tau fibrils and recapitulate features of tauopathy phenotypes including shared transcriptomic signatures, autophagic body accumulation, and reduced neuronal activity. A CRISPRi screen of genes associated with Tau pathobiology identified over 500 genetic modifiers of seeding-induced Tau propagation, including retromer VPS29 and genes in the UFMylation cascade. In progressive supranuclear palsy (PSP) and Alzheimer's Disease (AD) brains, the UFMylation cascade is altered in neurofibrillary-tangle-bearing neurons. Inhibiting the UFMylation cascade in vitro and in vivo suppressed seeding-induced Tau propagation. This model provides a robust platform to identify novel therapeutic strategies for 4R tauopathy.
Indexed as
Induced Pluripotent Stem CellsNeuronsTauopathiestau ProteinsAlzheimer DiseaseAnimalsAutophagyBrainCell DifferentiationHumansMiceMutationSupranuclear Palsy, ProgressiveMAPT protein, humantau ProteinsCRISPRi screenendolysosomehuman neuronsiPSCneurodegenerationneuronal activityretromerTautauopathyUFMylation
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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.