ArticleCell systems2021
Gene Regulatory Network Analysis and Engineering Directs Development and Vascularization of Multilineage Human Liver Organoids.
Article in Cell systems, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
What it found
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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.
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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.
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Who cites it
66 citing papers in PubMed, 99 citations in OpenAlex.
- A Proteomic Atlas of Human Milk: Uncovering Milk Functional Components.Research square · 2026Article
- New developments and applications of human organoids.Nature reviews. Molecular cell biology · 2026Review
- Synthetic developmental engineering of human liver organogenesis.Development (Cambridge, England) · 2026Review
- Construction of liver organoid models by hepatobiliary differentiation from human induced pluripotent stem cells: state of the art, challenges and improving strategies.Stem cell research & therapy · 2026Review
- Recent advances and expanding applications of organoid models in unveiling drug ADME profiles.Journal of pharmaceutical analysis · 2026Review
- Organoids in Pediatric Congenital Hepatobiliary Diseases: Current Status and Progress in Clinical Translational Research.Biomedicines · 2026Review
- Developmentally inspired synthetic kidney engineering.Nature biotechnology · 2026Review
- Monitoring biological effects of somatic cell genome editing.Nature reviews. Genetics · 2026Review
- Article
- Human organoids as 3D in vitro platforms for drug discovery: opportunities and challenges.Nature reviews. Drug discovery · 2026Review
- Global scientific trends in organoids from 2000 to 2024: a data-driven bibliometric and visualized analysis.International journal of surgery (London, England) · 2026Article
- Gene Editing of Pluripotent Stem Cell-Derived Hepatic Cells for Liver Disease Modeling and Therapeutic Development.Biomolecules & therapeutics · 2026Review
- Self-organization of sinusoidal vessels in pluripotent stem cell-derived human liver bud organoids.Nature biomedical engineering · 2025Article
- Elimination of CDX2 restricts intestinal hybrid differentiation signatures in stem cell-derived hepatocyte-like cells.Stem cell research & therapy · 2025Article
- Adenine base editing rescues disrupted BCKDH function and reduces BCAAs toxic accumulation in maple syrup urine disease patient iPSC-hepatic organoids.Stem cell research & therapy · 2025Article
- Designer mammalian living materials through genetic engineering.Bioactive materials · 2025Review
- Single-cell transcriptomics reveals liver developmental trajectory during lineage reprogramming of human induced hepatocyte-like cells.Cellular and molecular life sciences : CMLS · 2025Article
- Emerging biotechnologies for engineering liver organoids.Bioactive materials · 2025Review
- Advances in liver organoids: replicating hepatic complexity for toxicity assessment and disease modeling.Stem cell research & therapy · 2025Review
- Engineering the 3D structure of organoids.Stem cell reports · 2025Review
6 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
14 authors at 5 institutions in 2 countries.
Funding
Abstract
Pluripotent stem cell (PSC)-derived organoids have emerged as novel multicellular models of human tissue development but display immature phenotypes, aberrant tissue fates, and a limited subset of cells. Here, we demonstrate that integrated analysis and engineering of gene regulatory networks (GRNs) in PSC-derived multilineage human liver organoids direct maturation and vascular morphogenesis in vitro. Overexpression of PROX1 and ATF5, combined with targeted CRISPR-based transcriptional activation of endogenous CYP3A4, reprograms tissue GRNs and improves native liver functions, such as FXR signaling, CYP3A4 enzymatic activity, and stromal cell reactivity. The engineered tissues possess superior liver identity when compared with other PSC-derived liver organoids and show the presence of hepatocyte, biliary, endothelial, and stellate-like cell populations in single-cell RNA-seq analysis. Finally, they show hepatic functions when studied in vivo. Collectively, our approach provides an experimental framework to direct organogenesis in vitro by systematically probing molecular pathways and transcriptional networks that promote tissue development.
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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.