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Series GSE230519 Query DataSets for GSE230519
Status Public on Apr 15, 2024
Title Osteopontin drives neuroinflammation and cell loss in MAPT-N279K frontotemporal dementia patient neurons
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Frontotemporal dementia (FTD) is an incurable group of early-onset dementias that can be caused by 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, that 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.
 
Overall design Analysis of post-mortem human brain samples and iPSC neurons genomic information
Web link https://doi.org/10.1016/j.stem.2024.03.013
 
Contributor(s) Al-Dalahmah O, Lam M, McInvale JJ, Qu W, Nguyen T, Mun J, Kwon S, Ifediora N, Mahajan A, Humala N, Winters T, Angeles E, Jakubiak KA, Kühn R, Kim YA, De Rosa MC, Doege C, Paryani F, Flowers X, Dovas A, Mela A, Lu H, DeTure MA, Vonsattel JP, Wszolek ZK, Dickson DW, Kuhlmann T, Zaehres H, Schöler HR, Sproul AA, Siegelin MD, De Jager PL, Goldman JE, Menon V, Canoll P, Hargus G
Citation(s) 38626772
Submission date Apr 25, 2023
Last update date Jul 15, 2024
Contact name Osama Al Dalahmah
E-mail(s) oa2298@cumc.columbia.edu
Organization name Columbia University Irving Medical Center
Department Pathology & Cell Biology
Street address 622 West 168th Street
City New York
State/province NY
ZIP/Postal code 10032
Country USA
 
Platforms (1)
GPL24676 Illumina NovaSeq 6000 (Homo sapiens)
Samples (21)
GSM7225754 Postmortem human brain, FTD, HO001
GSM7225755 Postmortem human brain, FTD, GO004
GSM7225756 Postmortem human brain, FTD, GO006
This SubSeries is part of SuperSeries:
GSE230520 Osteopontin drives neuroinflammation and cell loss in MAPT-N279K frontotemporal dementia patient neurons
Relations
BioProject PRJNA961689

Download family Format
SOFT formatted family file(s) SOFTHelp
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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE230519_RAW.tar 291.8 Mb (http)(custom) TAR (of TXT)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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