ArticleCell stem cell2024
Osteopontin drives neuroinflammation and cell loss in MAPT-N279K frontotemporal dementia patient neurons.
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Article in Cell stem cell, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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25citing papers in PubMed
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Who cites it
25 citing papers in PubMed, 23 citations in OpenAlex.
- Article
- Context-dependent roles of osteopontin in aging-related neurological disorders.The Journal of international medical research · 2026Review
- Osteopontin in the Central Nervous System: Roles in Development, Injury, Neurodegeneration, and Neuro-Oncology.Biomolecules · 2026Review
- Preclinical serum alterations and tissue changes in protein and gene expression of early cerebrospinal fluid-validated biomarkers in scrapie.Veterinary research · 2026Article
- Low-intensity transcranial ultrasound neuromodulation promotes neuronal regeneration: A new hope for noninvasive treatment of neurodegenerative diseases.Neural regeneration research · 2026Article
- Review
- Review
- Aging-related matrix metallopeptidase 10 and osteopontin levels are associated with pathology, cognitive decline, and age at onset in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Macrophage plasticity and metabolic control in muscle repair and disease.Frontiers in immunology · 2026Review
- Decoding Dementia Mechanisms: Identification of Key Oligodendrocyte- Associated Genes through Integrative Bioinformatics and Machine Learning.Current topics in medicinal chemistry · 2026Article
- Regulatory T cells promote microglia-mediated synapse engulfment and functional recovery via the OPN-CD74 axis after spinal cord injury in mice.Journal of neuroinflammation · 2025Article
- Immunosenescence in aging and neurodegenerative diseases: evidence, key hallmarks, and therapeutic implications.Translational neurodegeneration · 2025Review
- Platelets regulate neural and oligodendroglial progenitors when infiltrating the brain parenchyma.Communications biology · 2025Article
- The Landscape of SPP1Immunology · 2025Review
- Optogenetic and Endogenous Modulation of CaInternational journal of molecular sciences · 2025Review
- Long-Term Neuroprotective Effects of Hydrogen-Rich Water and Memantine in Chronic Radiation-Induced Brain Injury: Behavioral, Histological, and Molecular Insights.Antioxidants (Basel, Switzerland) · 2025Article
- Exosomes in Regulating miRNAs for Biomarkers of Neurodegenerative Disorders.Molecular neurobiology · 2025Review
- OSBP Participates in Neural Damage Repair by Regulating Lysosome Transport Under Oxidative Stress.Molecular neurobiology · 2025Article
- Lab life, seasons and chromosome fusions affect non-cell-autonomously proliferation and neurogenesis, but not oligodendrogenesis, in mice and voles.Scientific reports · 2025Article
- Based exploration of the diagnostic value of oxidative stress-related key genes in chronic obstructive pulmonary disease.Cell biology and toxicology · 2025Article
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Authors and funding
36 authors at 5 institutions in 2 countries.
Osama Al-DalahmahDepartment of Pathology & Cell Biology, Columbia University, New York, NY 10032, USA; Taub Institute for Research on Alzheimer's Disease & the Aging Brain, Columbia University, New York, NY 10032, USA.
Matti LamCenter for Translational & Computational Neuroimmunology, Department of Neurology, Columbia University Irving Medical Center, New York, NY 10032, USA.
Julie J McInvaleDepartment of Pathology & Cell Biology, Columbia University, New York, NY 10032, USA.
Wenhui QuDepartment of Pathology & Cell Biology, Columbia University, New York, NY 10032, USA.
Trang NguyenDepartment of Pathology & Cell Biology, Columbia University, New York, NY 10032, USA.
Jeong-Yeon MunDepartment of Pathology & Cell Biology, Columbia University, New York, NY 10032, USA.
Sam KwonDepartment of Pathology & Cell Biology, Columbia University, New York, NY 10032, USA.
Nkechime IfedioraDepartment of Pathology & Cell Biology, Columbia University, New York, NY 10032, USA.
Aayushi MahajanDepartment of Neurosurgery, Columbia University, New York, NY 10032, USA.
Nelson HumalaDepartment of Neurosurgery, Columbia University, New York, NY 10032, USA.
Tristan WintersDepartment of Pathology & Cell Biology, Columbia University, New York, NY 10032, USA.
Ellen AngelesTaub Institute for Research on Alzheimer's Disease & the Aging Brain, Columbia University, New York, NY 10032, USA.
Kelly A JakubiakDepartment of Pathology & Cell Biology, Columbia University, New York, NY 10032, USA.
Rebekka KühnDepartment of Pathology & Cell Biology, Columbia University, New York, NY 10032, USA.
Yoon A KimDepartment of Pathology & Cell Biology, Columbia University, New York, NY 10032, USA.
Maria Caterina De RosaDivision of Molecular Genetics, Department of Pediatrics, Columbia University, New York, NY 10032, USA.
Claudia A DoegeDepartment of Pathology & Cell Biology, Columbia University, New York, NY 10032, USA.
Fahad ParyaniCenter for Translational & Computational Neuroimmunology, Department of Neurology, Columbia University Irving Medical Center, New York, NY 10032, USA.
Xena FlowersDepartment of Pathology & Cell Biology, Columbia University, New York, NY 10032, USA.
Athanassios DovasDepartment of Pathology & Cell Biology, Columbia University, New York, NY 10032, USA.
Angeliki MelaDepartment of Pathology & Cell Biology, Columbia University, New York, NY 10032, USA.
Hong LuDepartment of Pathology & Cell Biology, Columbia University, New York, NY 10032, USA.
Michael A DeTureDepartment of Neuroscience, The Mayo Clinic Florida, Jacksonville, FL 32224, USA.
Jean Paul VonsattelDepartment of Pathology & Cell Biology, Columbia University, New York, NY 10032, USA.
Zbigniew K WszolekDepartment of Neurology, The Mayo Clinic Florida, Jacksonville, FL 32224, USA.
Dennis W DicksonDepartment of Neuroscience, The Mayo Clinic Florida, Jacksonville, FL 32224, USA.
Tanja KuhlmannInstitute of Neuropathology, University Hospital Münster, Münster 48149, Germany.
Holm ZaehresInstitute of Anatomy, Ruhr University Bochum, Medical Faculty, Bochum 44801, Germany; Max Planck Institute for Molecular Biomedicine, Münster 48149, Germany.
Hans R SchölerMax Planck Institute for Molecular Biomedicine, Münster 48149, Germany.
Andrew A SproulDepartment of Pathology & Cell Biology, Columbia University, New York, NY 10032, USA; Taub Institute for Research on Alzheimer's Disease & the Aging Brain, Columbia University, New York, NY 10032, USA.
Markus D SiegelinDepartment of Pathology & Cell Biology, Columbia University, New York, NY 10032, USA.
Philip L De JagerTaub Institute for Research on Alzheimer's Disease & the Aging Brain, Columbia University, New York, NY 10032, USA; Center for Translational & Computational Neuroimmunology, Department of Neurology, Columbia University Irving Medical Center, New York, NY 10032, USA.
James E GoldmanDepartment of Pathology & Cell Biology, Columbia University, New York, NY 10032, USA; Taub Institute for Research on Alzheimer's Disease & the Aging Brain, Columbia University, New York, NY 10032, USA.
Vilas MenonTaub Institute for Research on Alzheimer's Disease & the Aging Brain, Columbia University, New York, NY 10032, USA; Center for Translational & Computational Neuroimmunology, Department of Neurology, Columbia University Irving Medical Center, New York, NY 10032, USA.
Peter CanollDepartment of Pathology & Cell Biology, Columbia University, New York, NY 10032, USA.
Gunnar HargusDepartment of Pathology & Cell Biology, Columbia University, New York, NY 10032, USA; Taub Institute for Research on Alzheimer's Disease & the Aging Brain, Columbia University, New York, NY 10032, USA. Electronic address: gh2374@cumc.columbia.edu.
Columbia University · USColumbia University Irving Medical Center · USJacksonville College · USMax Planck Institute for Molecular Biomedicine · DEUniversity Hospital Münster · DE
Funding
Technology and Remote Assessment CoreU19AG063911 · NIA · MAYO CLINIC ROCHESTER · PI ADAM L. BOXER, Bradley F Boeve · 2019 to 2026
$120.9MSatellite Diagnostic and Treatment Clinic CoreP50AG008702 · NIA · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI DE JAGER, PHILIP L · 1989 to 2019
$46.3MResearch Education CoreP30AG066462 · NIA · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI Miguel Arce · 2020 to 2026
$30.1MMedical Scientist Training ProgramT32GM145440 · NIGMS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI STEVEN L REINER · 2022 to 2026
$7.3MNeurology Research Education and Mentorship ProgramR25NS070697 · NINDS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI KUO, SHENG-HAN · 2010 to 2023
$1.9MElucidating the Role of Microglia and Neurotrophin Receptor p75 on Neuronal Degeneration in Frontotemporal DementiaK08NS116166 · NINDS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI HARGUS, GUNNAR · 2021 to 2025
$968kIdentifying shared and distinct cell type vulnerability across neurological diseases.R21AG075754 · NIA · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI AL DALAHMAH, OSAMA, GOLDMAN, JAMES · 2022 to 2022
$446kUsing a human stem cell model of tauopathy to evaluate the effects of tau filaments on cell metabolism at a single cell level in vitro and in vivoR21AG070414 · NIA · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI HARGUS, GUNNAR · 2020 to 2020
$446kApplication of single cell sequencing to study astrocyte-mediated neuronal degeneration in a stem cell model of frontotemporal dementiaR03NS112785 · NINDS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI HARGUS, GUNNAR · 2019 to 2020
$162kNIA NIH HHS P30 AG066462NIA NIH HHS P50 AG008702NIA NIH HHS R21 AG070414NIA NIH HHS R21 AG075754NIA NIH HHS U19 AG063911NIGMS NIH HHS T32 GM145440NINDS NIH HHS K08 NS116166NINDS NIH HHS R03 NS112785NINDS NIH HHS R25 NS070697
Abstract
Frontotemporal dementia (FTD) is an incurable group of early-onset dementias that can be caused by the deposition of hyperphosphorylated tau in patient brains. However, the mechanisms leading to neurodegeneration remain largely unknown. Here, we combined single-cell analyses of FTD patient brains with a stem cell culture and transplantation model of FTD. We identified disease phenotypes in FTD neurons carrying the MAPT-N279K mutation, which were related to oxidative stress, oxidative phosphorylation, and neuroinflammation with an upregulation of the inflammation-associated protein osteopontin (OPN). Human FTD neurons survived less and elicited an increased microglial response after transplantation into the mouse forebrain, which we further characterized by single nucleus RNA sequencing of microdissected grafts. Notably, downregulation of OPN in engrafted FTD neurons resulted in improved engraftment and reduced microglial infiltration, indicating an immune-modulatory role of OPN in patient neurons, which may represent a potential therapeutic target in FTD.
Indexed as
Frontotemporal DementiaNeuronsOsteopontintau ProteinsAnimalsHumansMiceMicrogliaMutationNeuroinflammatory DiseasesMAPT protein, humanOsteopontintau Proteinsdisease modelingfrontotemporal dementiaFTDinduced pluripotent stem cellsMAPT N279KmicroglianeuroinflammationOPNosteopontinsingle nucleus RNA sequencingsnRNA-seqSpp1Tautransplantation
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