ArticleNature communications2024
Mapping of mitogen and metabolic sensitivity in organoids defines requirements for human hepatocyte growth.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 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
24 citing papers in PubMed.
- Transient culture of adult human hepatocytes as organoids improves engineered liver engraftment.Biomaterials · 2027Article
- Reverse bioengineering of the liver: developmental principles for next-generation liver-on-a-chip systems.Communications biology · 2026Review
- Endodermal Organoids Along Two Axes: Single-Organ Fidelity, Inter-Organ Reconstruction, and the Unbuilt Gut-Lung Frontier.Stem cell reviews and reports · 2026Review
- Liver Organoids: From Disease Modelling to Regenerative Medicine.Cell proliferation · 2026Review
- Synthetic developmental engineering of human liver organogenesis.Development (Cambridge, England) · 2026Review
- Single-cell transcriptomic comparison of tubular segment maturation in advanced humaniScience · 2026Article
- Developing a Clinically Practical Biomaterial Platform for Endogenous Liver Regeneration.Gels (Basel, Switzerland) · 2026Review
- Paracrine Factor Local Gradient-Generating System for Engineering Perfusable Vascularized Hepatocyte Tissues with Perfusion-Induced Proliferation.Advanced healthcare materials · 2026Article
- Automated and scalable expansion of human liver organoids for translational applications.Journal of translational medicine · 2026Article
- Synthetic control of implanted engineered liver tissue growth.Science advances · 2026Article
- Three-dimensional bioprinted hiHeps hepatorganoids with enhanced hepatic functions for the treatment of liver failure and promotion of liver regeneration.Bioactive materials · 2026Article
- Generation of proliferative hESC-derived grape-clustered hepatocyte organoids with multipolar architecture as regenerative counterpart via synergy of YAP and IGF2 pathways.Cell death & disease · 2026Article
- Organoids for Metabolic Disease Modeling.Journal of inherited metabolic disease · 2026Review
- Article
- Review
- Modeling pathogenesis and progression of metabolic dysfunction-associated steatotic liver disease and therapeutic drug screening using hESC-derived mature polarized hepatocyte organoids.Stem cell research & therapy · 2025Article
- Single-cell sequencing and organoids: applications in organ development and disease.Molecular biomedicine · 2025Review
- Construction of vascularized liver microtissues recapitulates angiocrine-mediated hepatocytes maturation and enhances therapeutic efficacy for acute liver failure.Bioactive materials · 2025Article
- Large-Scale Production of Expandable Hepatoblast Organoids and Polarised Hepatocyte Organoids From hESCs Under 3D Static and Dynamic Suspension Conditions.Cell proliferation · 2025Article
- Crosstalk Between Dietary Fatty Acids and MicroRNAs in the Regulation of Hepatic ApoB-Containing Lipoprotein Synthesis in Humans.International journal of molecular sciences · 2025Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mechanisms underlying human hepatocyte growth in development and regeneration are incompletely understood. In vitro, human fetal hepatocytes (FH) can be robustly grown as organoids, while adult primary human hepatocyte (PHH) organoids remain difficult to expand, suggesting different growth requirements between fetal and adult hepatocytes. Here, we characterize hepatocyte organoid outgrowth using temporal transcriptomic and phenotypic approaches. FHs initiate reciprocal transcriptional programs involving increased proliferation and repressed lipid metabolism upon initiation of organoid growth. We exploit these insights to design maturation conditions for FH organoids, resulting in acquisition of mature hepatocyte morphological traits and increased expression of functional markers. During PHH organoid outgrowth in the same culture condition as for FHs, the adult transcriptomes initially mimic the fetal transcriptomic signatures, but PHHs rapidly acquire disbalanced proliferation-lipid metabolism dynamics, resulting in steatosis and halted organoid growth. IL6 supplementation, as emerged from the fetal dataset, and simultaneous activation of the metabolic regulator FXR, prevents steatosis and promotes PHH proliferation, resulting in improved expansion of the derived organoids. Single-cell RNA sequencing analyses reveal preservation of their fetal and adult hepatocyte identities in the respective organoid cultures. Our findings uncover mitogen requirements and metabolic differences determining proliferation of hepatocytes changing from development to adulthood.
Indexed as
Identifiers
What Socratic 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 Socratic graph.