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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]

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

PROVIDER: PRJNA1126390 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR29481330.fastq.gz	Fastqsanger.gz
	SRR29481331.fastq.gz	Fastqsanger.gz

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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

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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.

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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.

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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: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.

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

Project description:This SuperSeries is composed of the SubSeries listed below.

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

Project description:In fetal development, tissue interaction such as the interplay between blood vessel (BV) and epithelial tissue is crucial for organogenesis. Here we recapitulate the spatial arrangement between liver epithelial tissue and the portal vein to observe the formation of intrahepatic bile ducts (BDs) from human induced pluripotent stem cells (hiPSC). We co-culture hiPSC-liver progenitors on the artificial BV consisting of immature smooth muscle cells and endothelial cells, both derived from hiPSCs. After 3 weeks, liver progenitors within hiPSC-BV-incorporated liver organoids (BVLO) differentiate to cholangiocytes and acquire epithelial characteristics, including intercellular junctions, microvilli on the apical membrane, and secretory functions. Furthermore, liver surface transplanted-BVLO temporarily attenuates cholestatic injury symptoms. Single cell RNA sequence analysis suggests that BD interact with the BV in BVLO through TGFβ and Notch pathways. Knocking out JAG1 in hiPSC-BV significantly attenuates bile duct formation, highlighting BVLO potential as a model for Alagille syndrome, a congenital biliary disease. Overall, we develop a novel 3D co-culture method that successfully establishes functional human BDs by emulating liver epithelial-BV interaction.

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