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A human iPSC model of Tauopathies engineered for 4R Tau isoform expression endogenously develops late-stage neuronal Tau pathology

GSE311009 Homo sapiens (human) RNA-seq (gene expression) 36 samples Submitted 2026/01/26 Platform GPL28337
At a glance

RNA-seq (gene expression) · human · 36 samples

What it is
RNA-seq (gene expression)Gene activity measured by sequencing. The summary does not mention single-cell work, so this is most likely bulk: one average per sample, the usual starting point for comparing groups.
Organism
Homo sapiens (human)
Samples
36 samples: 12 conditions, mostly in triplicateGroups are read from the sample names, not from the paper. Check the list below.
Data you can get
A processed table (series matrix) and supplementary files from NCBI; the raw sequencing reads from ENA. Which of these hold counts depends on the study, so check the file list.
Paper
A human iPSC model of tauopathies engineered for 4R tau isoform expression endogenously develops late-stage neuronal tau pathologyScience translational medicine · 2026
Summary (written by the submitters)
Tauopathies, such as Alzheimer’s disease and Frontotemporal Dementia, are common neurodegenerative diseases characterized by misfolding, hyperphosphorylation, and aggregation of Tau. Molecular mechanisms underlying Tauopathies are still poorly understood, which is in part due to a lack of human models autonomously developing major disease hallmarks.
Read the full summary ↓
Formation of late-stage disease phenotypes may require adult Tau isoform expression, which contributes to Tau pathogenesis but is challenging to replicate in human stem-cell-derived systems, thus impeding research on underlying mechanisms and drug development. Here we show that induction of adult human brain-like 4R Tau isoform expression enables cell-intrinsic formation of late-stage Tauopathy hallmarks in iPSC-derived neurons engineered to contain synergistic Tau mutations, without exogenous sources of Tau pathology. Neurons accumulated seeding-competent, hyper-phosphorylated, fibrillar Tau in tangle-like structures. Furthermore, exclusive expression of mutant 4R in the absence of the 3R Tau isoform disproportionately intensified pathology, resulting in highly abundant Tau misfolding and aggregation. Finally, we provide proof-of-principle that our model can be translationally applied both to test chemical disease modulators and evaluate human Tau PET tracers. Collectively, our model corroborates the central role of 4R Tau isoform expression for pathogenesis in human neurons and enables novel investigations to elucidate mechanisms underlying human Tauopathy formation. Moreover, it may also serve as a platform supporting urgently needed development of disease-modifying drugs.
Published in
A human iPSC model of tauopathies engineered for 4R tau isoform expression endogenously develops late-stage neuronal tau pathology
Dannert A, Schulz N, Klimmt J et al. · Science translational medicine 2026 · PMID 41950304 · doi:10.1126/scitranslmed.adu9845
This dataset
Open GSE311009 in finder → Find more human RNA-seq datasets →
Download · which file do I need?

Direct links to NCBI and ENA, no account and no request form. Pick by what you want to do: take the small processed table to look, the supplementary files to re-analyse, or the original raw data to start over.

1 · Just have a look

Processed table

The series matrix: one table of values per sample as the submitters processed it. The smallest download, and it opens in Excel or R. Start here to see what the data look like.

Series matrix ↓
2 · Re-analyse it

Supplementary files

The count tables and other files the authors uploaded. Take only the samples you need, or the whole study as GSE311009_RAW.tar (it can run to tens of gigabytes).

All supplementary files ↗ Whole study · RAW.tar ↓
3 · Start from the raw reads

Raw sequencing reads

The original FASTQ files, straight from the sequencer, held at ENA. Large, and you align them yourself, so only choose this if you need to re-process the study from scratch.

Raw reads on ENA ↗

What the files usually look like: For RNA-seq the counts are usually a table among the supplementary files (look for 'counts', 'expression', 'FPKM' or 'TPM' in the file name). The series matrix of a sequencing study is sometimes nearly empty.

Also filed as BioProject PRJNA1368479 and SRA study SRP648689. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41950304) ↗
Study design
12 conditions, mostly in triplicate
WT cells, DIV15, ×3 WT cells, DIV35, ×3 4R PLSF-hom cells, DIV15, ×3 4R PLSF-hom cells, DIV35, ×3 WT cells, Nocodoazole treated, DIV15, ×3 WT cells, Nocodoazole treated, DIV35, ×3 PLSF cells, DIV15, ×3 PLSF cells, DIV35, ×3 +4 more

Supports a between-group comparison across 36 samples.

How we read this: 12 replicated groups read from 36 sample titles; they account for 36 of them. These groups are guessed from the sample names, not taken from the paper, so check them against the sample list below before relying on them.

Samples in this study
Datasets on a similar topic

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