ArticleThe EMBO journal2022
Gruffi: an algorithm for computational removal of stressed cells from brain organoid transcriptomic datasets.
Article in The EMBO journal, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers, 1 of them a synthesis that pooled it.
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Who cites it
54 citing papers in PubMed, 1 synthesis or guideline pooled 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
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- Label-free biochemical imaging and time point analysis of neural organoids via deep learning-enhanced Raman microspectroscopy.Science advances · 2026Article
- α-Synuclein blocks endoplasmic reticulum co-translational protein translocation early in Parkinson's disease.Nature communications · 2026Article
- Human amygdala-like telencephalic organoids model stress circuitry in assembloid systems.Cell stem cell · 2026Article
- Brain Organoids: Emerging Platforms for Modern Neuroscience.Brain sciences · 2026Review
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- Human cortical organoids recapitulate inter-individual variability in infant brain-growth trajectories.Cell stem cell · 2026Article
- AI and organoid platforms for brain-targeted theranostics.Theranostics · 2026Review
- MeCP2 regulates telencephalic development in human cerebral organoids.Cell reports · 2025Article
- SETD1A regulates psychiatric gene networks involved in genomic stability and synaptic function in rare and sporadic schizophrenia.Nature communications · 2025Article
- Single molecule nanopore counting assay targeting small extracellular vesicle cargo for non-invasive monitoring of cerebral organoid development and health.Scientific reports · 2025Article
- Glucose and Oxygen Metabolism Coordinate Human Cortical Developmental Decisions.bioRxiv : the preprint server for biology · 2025Article
- A phenotypic brain organoid atlas and biobank for neurodevelopmental disorders.Cell stem cell · 2025Article
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- Scalable production of human cortical organoids using a biocompatible polymer.Nature biomedical engineering · 2025Article
- Single rosette-based generation of uniform cortical assembloids recapitulating cellular interactions between neurons and glial cells.Nature communications · 2025Article
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Authors and funding
10 authors.
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No grant is acknowledged in the PubMed record.
Abstract
Organoids enable in vitro modeling of complex developmental processes and disease pathologies. Like most 3D cultures, organoids lack sufficient oxygen supply and therefore experience cellular stress. These negative effects are particularly prominent in complex models, such as brain organoids, and can affect lineage commitment. Here, we analyze brain organoid and fetal single-cell RNA sequencing (scRNAseq) data from published and new datasets, totaling about 190,000 cells. We identify a unique stress signature in the data from all organoid samples, but not in fetal samples. We demonstrate that cell stress is limited to a defined subpopulation of cells that is unique to organoids and does not affect neuronal specification or maturation. We have developed a computational algorithm, Gruffi, which uses granular functional filtering to identify and remove stressed cells from any organoid scRNAseq dataset in an unbiased manner. We validated our method using six additional datasets from different organoid protocols and early brains, and show its usefulness to other organoid systems including retinal organoids. Our data show that the adverse effects of cell stress can be corrected by bioinformatic analysis for improved delineation of developmental trajectories and resemblance to in vivo data.
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