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Generation of 3D tubular bile duct within human iPSC-derived liver organoid by incorporating human iPSC-derived blood vessel

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE240534 | GEO | 2024/07/16

REPOSITORIES: GEO

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Generation of 3D tubular bile duct within human iPSC-derived liver organoid by incorporating human iPSC-derived blood vessel [scRNA-Seq]

Project description:Bile duct (BD) structure is crucial for bile secretion to maintain liver homeostasis. Although several human induced pluripotent stem cell (hiPSC)-derived liver organoids have been generated, no study recapitulates the development of BD tubules. Here, we focus on an environmental cue to form tubular BDs, specifically the interaction between liver progenitors with the portal vein (PV). We co-culture hiPSC-liver progenitors with PV-like hiPSC-blood vessel (hiPSC-BV) which consists of immature hiPSC-smooth muscle cells (SMC) with a similar character to fetal PV-SMC. After two weeks, liver progenitors within hiPSC-BV-integrated liver organoid (BVLO) differentiate into the cholangiocyte-lineage and establish tubular structures with epithelial characteristics including intercellular junctions, microvilli on the apical membrane, and secretory functions. Liver surface transplanted BVLO showed further BD maturation and connection to the host BD. Taken together, our study developed a novel 3D co-culture methodo establish functional human tubular BDs by recapitulating PV-BD interaction.

2024-07-16 | GSE270413 | GEO

Generation of 3D tubular bile duct within human iPSC-derived liver organoid by incorporating human iPSC-derived blood vessel [RNA-seq]

Project description:Bile duct (BD) structure is crucial for bile secretion to maintain liver homeostasis. Although several human induced pluripotent stem cell (hiPSC)-derived liver organoids have been generated, no study recapitulates the development of BD tubules. Here, we focus on an environmental cue to form tubular BDs, specifically the interaction between liver progenitors with the portal vein (PV). We co-culture hiPSC-liver progenitors with PV-like hiPSC-blood vessel (hiPSC-BV) which consists of immature hiPSC-smooth muscle cells (SMC) with a similar character to fetal PV-SMC. After two weeks, liver progenitors within hiPSC-BV-integrated liver organoid (BVLO) differentiate into the cholangiocyte-lineage and establish tubular structures with epithelial characteristics including intercellular junctions, microvilli on the apical membrane, and secretory functions. Liver surface transplanted BVLO showed further BD maturation and connection to the host BD. Taken together, our study developed a novel 3D co-culture method o establish functional human tubular BDs by recapitulating PV-BD interaction.

2024-07-16 | GSE198888 | GEO

Generation of 3D tubular bile duct within human iPSC-derived liver organoid by incorporating human iPSC-derived blood vessel [scRNA-seq]

Project description:The tubular structure of the intrahepatic bile duct (BD) is crucial for its physiological functions including bile excretion. Although several human induced pluripotent stem cell (hiPSC)-derived liver organoids were generated, no prior study could emulate the development of BD tubules. Here we focus on the environmental cue to initiate BD development, specifically the interaction between liver progenitors and the portal vein (PV). We co-cultured hiPSC-liver progenitors with hiPSC-blood vessels (hiPSC-BV) consisting of immature hiPSC-smooth muscle cells (SMC) expressing JAG1, a key factor for cholangiocyte induction. After three weeks, liver progenitors within hiPSC-BV-integrated liver organoids (BVLO) differentiate into cholangiocyte lineage and establish tubular structures with epithelial characteristics, including intercellular junctions, microvilli on the apical membrane, and secretory functions. Furthermore, liver surface transplanted-BVLO demonstrated BD graft-host connection and suggested therapeutical potential. Overall, we developed a novel 3D co-culture method to establish functional human tubular BDs by emulating PV-BD interaction.

2024-07-16 | GSE240019 | GEO

Generation of 3D tubular bile duct within human iPSC-derived liver organoid by incorporating human iPSC-derived blood vessel

Project description:Generation of 3D tubular bile duct within human iPSC-derived liver organoid by incorporating human iPSC-derived blood vessel

| PRJNA1004192 | ENA

Generation of 3D tubular bile duct within human iPSC-derived liver organoid by incorporating human iPSC-derived blood vessel [scRNA-Seq]

Project description:Generation of 3D tubular bile duct within human iPSC-derived liver organoid by incorporating human iPSC-derived blood vessel [scRNA-Seq]

| PRJNA1126390 | ENA

Generation of 3D tubular bile duct within human iPSC-derived liver organoid by incorporating human iPSC-derived blood vessel [RNA-seq]

Project description:Generation of 3D tubular bile duct within human iPSC-derived liver organoid by incorporating human iPSC-derived blood vessel [RNA-seq]

| PRJNA817246 | ENA

Generation of 3D tubular bile duct within human iPSC-derived liver organoid by incorporating human iPSC-derived blood vessel [scRNA-seq]

Project description:Generation of 3D tubular bile duct within human iPSC-derived liver organoid by incorporating human iPSC-derived blood vessel [scRNA-seq]

| PRJNA1001928 | ENA

Human liver organoid derived intra-hepatic bile duct cells support SARS-CoV-2 infection and replication.

Project description:Although the main route of infection for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the respiratory tract, liver injury is also commonly seen in many patients, as evidenced by deranged parenchymal liver enzymes. Furthermore, the severity of liver damage has been shown to correlate with higher mortality. Overall, the mechanism behind the liver injury remains unclear. We showed in this study that intra-hepatic bile duct cells could be grown using a human liver organoid platform. The cholangiocytes were not only susceptible to SARS-CoV-2 infection, they also supported efficient viral replication. We also showed that SARS-CoV-2 replication was much higher than SARS-CoV. Our findings suggested direct cytopathic viral damage being a mechanism for SARS-CoV-2 liver injury.

| S-EPMC8965546 | biostudies-literature

Tubular bile duct structure mimicking bile duct morphogenesis for prospective in vitro liver metabolite recovery.

Project description:BackgroundLiver metabolites are used to diagnose disease and examine drugs in clinical pharmacokinetics. Therefore, development of an in vitro assay system that reproduces liver metabolite recovery would provide important benefits to pharmaceutical research. However, liver models have proven challenging to develop because of the lack of an appropriate bile duct structure for the accumulation and transport of metabolites from the liver parenchyma. Currently available bile duct models, such as the bile duct cyst-embedded extracellular matrix (ECM), lack any morphological resemblance to the tubular morphology of the living bile duct. Moreover, these systems cannot overcome metabolite recovery issues because they are established in isolated culture systems. Here, we successfully established a non-continuous tubular bile duct structure model in an open-culture system, which closely resembled an in vivo structure. This system was utilized to effectively collect liver metabolites separately from liver parenchymal cells.ResultsTriple-cell co-culture of primary rat hepatoblasts, rat biliary epithelial cells, and mouse embryonic fibroblasts was grown to mimic the morphogenesis of the bile duct during liver development. Overlaying the cells with ECM containing a Matrigel and collagen type I gel mixture promoted the development of a tubular bile duct structure. In this culture system, the expression of specific markers and signaling molecules related to biliary epithelial cell differentiation was highly upregulated during the ductal formation process. This bile duct structure also enabled the separate accumulation of metabolite analogs from liver parenchymal cells.ConclusionsA morphogenesis-based culture system effectively establishes an advanced bile duct structure and improves the plasticity of liver models feasible for autologous in vitro metabolite-bile collection, which may enhance the performance of high-throughput liver models in cell-based assays.

| S-EPMC7081557 | biostudies-literature

Application of an iPSC-Derived Organoid Model for Localized Scleroderma Therapy.

Project description:Localized scleroderma (LoS) is a rare chronic disease with extensive tissue fibrosis, inflammatory infiltration, microvascular alterations, and epidermal appendage lesions. However, a deeper understanding of the pathogenesis and treatment strategies of LoS is currently limited. In the present work, a proteome map of LoS skin is established, and the pathological features of LoS skin are characterized. Most importantly, a human-induced pluripotent stem cell-derived epithelial and mesenchymal (EM) organoids model in a 3D culture system for LoS therapy is established. According to the findings, the application of EM organoids on scleroderma skin can significantly reduce the degree of skin fibrosis. In particular, EM organoids enhance the activity of epidermal stem cells in the LoS skin and promotes the regeneration of sweat glands and blood vessels. These results highlight the potential application of organoids for promoting the recovery of scleroderma associated phenotypes and skin-associated functions. Furthermore, it can provide a new therapeutic alternative for patients suffering from disfigurement and skin function defects caused by LoS.

| S-EPMC9165518 | biostudies-literature

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