ArticleNature neuroscience2021
Human ALS/FTD brain organoid slice cultures display distinct early astrocyte and targetable neuronal pathology.
Article in Nature neuroscience, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 123 papers, 4 of them syntheses that pooled it.
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Who cites it
123 citing papers in PubMed, 4 syntheses or guidelines pooled it, 159 citations in OpenAlex.
- Mapping the Cerebral Organoid Landscape: A Systematic Review of Preclinical 3D Models in Neuroscience.Advanced healthcare materials · 2026Pooled it
- Modelling mitochondrial diseases in neuronsJournal of neuromuscular diseases · 2025Pooled it
- Meta-analysis of single-cell RNA sequencing co-expression in human neural organoids reveals their high variability in recapitulating primary tissue.PLoS biology · 2024Pooled it
- Bibliometric and visual analysis of single-cell multiomics in neurodegenerative disease arrest studies.Frontiers in neurology · 2024Pooled it
- Rapid generation of human sensory neurons from iPSC for modeling of peripheral neuropathies.Journal of neuroscience methods · 2026Article
- Review
- Using human 3D organoid models to gain mechanistic insight in motor neuron diseases.Nature reviews. Neuroscience · 2026Review
- Roles of autophagy in brain homeostasis and disease.Nature neuroscience · 2026Review
- Glial cell toxicity in a Drosophila C9orf72 neurodegeneration model.PLoS genetics · 2026Article
- Neural Organoid Models as a Platform for Studying Disease Mechanisms in Amyotrophic Lateral Sclerosis.Journal of neurochemistry · 2026Review
- Brain organoids and genome editing: A new era in understanding human brain development and disorders.Neural regeneration research · 2026Article
- A human corticospinal organoid-slice connectoid model informs enhancer strategies for post-injury axon regrowth.Cell reports · 2026Article
- Mitochondrial DNA heteroplasmy drives cortical neuronal disturbances in human organoids harbouring the common m.3243A>G mutation.Nature communications · 2026Article
- Endoplasmic reticulum stress in disease pathogenesis: its implications for therapy.Signal transduction and targeted therapy · 2026Review
- Gene Targeted Therapies for Neurodegenerative Disorders: Strategies and Implications in ALS and SMA.Genes · 2026Review
- Human organoids as 3D in vitro platforms for drug discovery: opportunities and challenges.Nature reviews. Drug discovery · 2026Review
- Review
- Frontotemporal dementia patient-derived iPSC neurons show cell pathological hallmarks and evidence for synaptic dysfunction and DNA damage.Molecular psychiatry · 2026Article
- Review
- Multiscale 3D microfluidic platform for intraorganoid delivery.Research square · 2026Article
63 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
Abstract
Amyotrophic lateral sclerosis overlapping with frontotemporal dementia (ALS/FTD) is a fatal and currently untreatable disease characterized by rapid cognitive decline and paralysis. Elucidating initial cellular pathologies is central to therapeutic target development, but obtaining samples from presymptomatic patients is not feasible. Here, we report the development of a cerebral organoid slice model derived from human induced pluripotent stem cells (iPSCs) that recapitulates mature cortical architecture and displays early molecular pathology of C9ORF72 ALS/FTD. Using a combination of single-cell RNA sequencing and biological assays, we reveal distinct transcriptional, proteostasis and DNA repair disturbances in astroglia and neurons. We show that astroglia display increased levels of the autophagy signaling protein P62 and that deep layer neurons accumulate dipeptide repeat protein poly(GA), DNA damage and undergo nuclear pyknosis that could be pharmacologically rescued by GSK2606414. Thus, patient-specific iPSC-derived cortical organoid slice cultures are a reproducible translational platform to investigate preclinical ALS/FTD mechanisms as well as novel therapeutic approaches.
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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.