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Multi-Zonal Liver Organoids from Stem Cells
- Researchers have successfully engineered multi-zonal liver organoids from human pluripotent stem cells, mimicking the liver's spatial architecture.
- The challenge of replicating the liver's zonal heterogeneity in vitro has been addressed through self-assembling organoids derived from human induced pluripotent stem cells.
- Ascorbate and bilirubin were used to differentiate hepatic progenitors into zone-specific phenotypes, creating a spatially ordered microtissue.
- The organoids authentically recapitulate the multi-zonal hepatic architecture, allowing for physiologically relevant studies in liver biology and regenerative medicine.
- Single-nucleus RNA sequencing highlighted the gene expression landscapes across individual nuclei within the organoids, revealing zonal identities.
- Epigenetic analyses uncovered regulatory mechanisms involving molecules like ascorbate and bilirubin that shape chromatin accessibility and gene expression specific to zonal phenotypes.
- The zonally patterned hepatic organoids demonstrated zone-specific metabolic activities, paving the way for accurate modeling of liver metabolism and diseases.
- Transplantation of human organoids improved survival outcomes in rats with liver injury, showcasing the potential for novel cell therapies in chronic liver diseases.
- The model offers insights into liver development, zonal specification, drug toxicity screening, and disease pathogenesis.
- This innovative technology opens new possibilities for drug discovery, personalized medicine, and advancing liver health through bioengineered grafts.
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