ArticleGenome biology2023
In-organoid single-cell CRISPR screening reveals determinants of hepatocyte differentiation and maturation.
Article in Genome biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 22 citations in OpenAlex.
- High-Content CRISPR Screening: Methods and Applications.MedComm · 2026Review
- Patient-Derived Organoid-Based CRISPR Screens in Cancer Research: Applications, Advances, and Challenges.Cancer medicine · 2026Review
- Single-Cell CRISPR: An Efficient Strategy for Decoding Plant Cis-Regulatory Complexity.Plant biotechnology journal · 2026Review
- Lessons on multicellular two- (2D) and three-dimensional (3D) culture in parasitology: Insights, challenges and future directions.International journal for parasitology · 2026Review
- MIC-Drop-seq: scalable single-cell phenotyping of mutant vertebrate embryos.Nature communications · 2026Article
- Harnessing induced pluripotent stem cells and organoids for disease modeling and precision medicine.Stem cell research & therapy · 2026Review
- ClinMAVE: a curated database for clinical application of data from multiplexed assays of variant effect.Nucleic acids research · 2026Article
- Multiscale Construction, Evaluation, and Application of Organoids.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Nutritional c-Fos Induction Rewires Hepatic Metabolism and Can Promote Obesity-Associated Hepatocellular Carcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- RNA binding protein DDX3X drives pancreatic cancer progression via the TLE2-MYL9 axis.Science advances · 2025Article
- Large-scale CRISPR screening in primary human 3D gastric organoids enables comprehensive dissection of gene-drug interactions.Nature communications · 2025Article
- CRISPR/Cas technologies in pancreatic cancer research and therapeutics: recent advances and future outlook.Discover oncology · 2025Review
- Barcoded monoclonal embryoids are a potential solution to confounding bottlenecks in mosaic organoid screens.bioRxiv : the preprint server for biology · 2025Article
- Perturbomics: CRISPR-Cas screening-based functional genomics approach for drug target discovery.Experimental & molecular medicine · 2025Review
- Developments and Applications of Liver-on-a-Chip Technology-Current Status and Future Prospects.Biomedicines · 2025Review
- Integration of Organoids With CRISPR Screens: A Narrative Review.Biology of the cell · 2025Review
- A stage specific NETs-related signature in alcoholic steatohepatitis: from molecular subtyping to therapeutic vulnerabilities.Frontiers in immunology · 2025Article
- Analyzing the functional effects of DNA variants with gene editing.Cell reports methods · 2024Review
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundHarnessing hepatocytes for basic research and regenerative medicine demands a complete understanding of the genetic determinants underlying hepatocyte differentiation and maturation. Single-cell CRISPR screens in organoids could link genetic perturbations with parallel transcriptomic readout in single cells, providing a powerful method to delineate roles of cell fate regulators. However, a big challenge for identifying key regulators during data analysis is the low expression levels of transcription factors (TFs), which are difficult to accurately estimate due to noise and dropouts in single-cell sequencing. Also, it is often the changes in TF activities in the transcriptional cascade rather than the expression levels of TFs that are relevant to the cell fate transition.
resultsHere, we develop Organoid-based Single-cell CRISPR screening Analyzed with Regulons (OSCAR), a framework using regulon activities as readouts to dissect gene knockout effects in organoids. In adult-stem-cell-derived liver organoids, we map transcriptomes in 80,576 cells upon 246 perturbations associated with transcriptional regulation of hepatocyte formation. Using OSCAR, we identify known and novel positive and negative regulators, among which Fos and Ubr5 are the top-ranked ones. Further single-gene loss-of-function assays demonstrate that Fos depletion in mouse and human liver organoids promote hepatocyte differentiation by specific upregulation of liver metabolic genes and pathways, and conditional knockout of Ubr5 in mouse liver delays hepatocyte maturation.
conclusionsAltogether, we provide a framework to explore lineage specifiers in a rapid and systematic manner, and identify hepatocyte determinators with potential clinical applications.
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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.