Project description: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 [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 method o establish functional human tubular BDs by recapitulating PV-BD interaction.
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.
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.
Project description:We established the expansion culture of human iPSC-derived ureteric bud tip cells (UBTCs), an embryonic precursor that give rise to collecting ducts (CDs), and succeeded in advancing the developmental stage of CD organoids. We used single cell RNA-sequencing (scRNA-seq) to dissect cell types in CD organoids.
Project description:Investigate the functional capabilities of human iPSC-derived liver organoids generated on Matrigel or self-assembed in rotating wall vessel (RWV) via bulk RNA-seq, RT-qPCR and immunostaining, to provide a simple and high-throughput way to generate Matrigel-free liver organoids for research and clinical applications