ArticleActa neuropathologica2023
Cryptic exon detection and transcriptomic changes revealed in single-nuclei RNA sequencing of C9ORF72 patients spanning the ALS-FTD spectrum.
Article in Acta neuropathologica, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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.
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.
Who cites it
36 citing papers in PubMed, 49 citations in OpenAlex.
- Integrative synaptosome multi-omics reveals disrupted synapse organization and localized cryptic transcripts in C9ORF72-frontotemporal dementia.Acta neuropathologica · 2026Article
- Distinct cellular phenotypes of language and executive decline in amyotrophic lateral sclerosis.Cell · 2026Article
- Article
- Single-cell transcriptomic atlas of frontoinsular cortex reveals molecular correlates of selective neuronal vulnerability in FTD.bioRxiv : the preprint server for biology · 2026Article
- An expanded cortical map of von Economo neurons in the human medial prefrontal cortex.Cerebral cortex (New York, N.Y. : 1991) · 2026Article
- Single-nucleus multiome analysis in the human prefrontal cortex identifies gene expression and cis-regulatory elements associated with aging.Cell reports · 2026Article
- Splicing the narrative: alternative TARDBP splicing and its relation to neurodegeneration in ALS and FTD.The Journal of clinical investigation · 2026Review
- Decoding neurodegeneration one cell at a time.The Journal of clinical investigation · 2026Review
- Multi-modal dissection of cell-type specific TDP-43 pathology in the motor cortex.Nature communications · 2026Article
- A quantitative cell-based reporter links TDP-43 aggregation and dysfunction to define pathogenic mechanisms.PLoS biology · 2026Article
- Aberrant Splicing Signatures Underpin Oligodendrocyte Damage in ALS and Neuron Loss in FTD.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Article
- Transcriptomic and pathological analysis of the hnRNP network reveals glial involvement in frontotemporal lobar degeneration pathological subtypes.Brain communications · 2026Article
- Single-nucleus transcriptome atlas of orbitofrontal cortex in ALS with a deep learning-based decoding of alternative polyadenylation mechanisms.Cell genomics · 2025Article
- Sensitivity to TDP-43 loss and degradation resistance determine cryptic exon biomarker potential.bioRxiv : the preprint server for biology · 2025Article
- TDP-43 loss induces cryptic polyadenylation in ALS/FTD.Nature neuroscience · 2025Article
- TDP-43 nuclear loss in FTD/ALS causes widespread alternative polyadenylation changes.Nature neuroscience · 2025Article
- Integrative Transcriptomic and Network-Based Analysis of Neuromuscular Diseases.International journal of molecular sciences · 2025Article
- Article
- Cryptic splicing in synaptic and membrane excitability genes links TDP-43 loss to neuronal dysfunction.bioRxiv : the preprint server for biology · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
The C9ORF72-linked diseases amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are characterized by the nuclear depletion and cytoplasmic accumulation of TAR DNA-binding protein 43 (TDP-43). Recent studies have shown that the loss of TDP-43 function leads to the inclusion of cryptic exons (CE) in several RNA transcript targets of TDP-43. Here, we show for the first time the detection of CEs in a single-nuclei RNA sequencing (snRNA-seq) dataset obtained from frontal and occipital cortices of C9ORF72 patients that phenotypically span the ALS-FTD disease spectrum. We assessed each cellular cluster for detection of recently described TDP-43-induced CEs. Transcripts containing CEs in the genes STMN2 and KALRN were detected in the frontal cortex of all C9ORF72 disease groups with the highest frequency in excitatory neurons in the C9ORF72-FTD group. Within the excitatory neurons, the cluster with the highest proportion of cells containing a CE had transcriptomic similarities to von Economo neurons, which are known to be vulnerable to TDP-43 pathology and selectively lost in C9ORF72-FTD. Differential gene expression and pathway analysis of CE-containing neurons revealed multiple dysregulated metabolic processes. Our findings reveal novel insights into the transcriptomic changes of neurons vulnerable to TDP-43 pathology.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.