Project description:Kidney organoids are ideal models to study the complex process of human kidney development. Here we report the generation of functional kidney organoids by reprogramming human urine epithelial cells (hUCs). RNA-seq and ATAC-seq revealed the three-stage process of the 2D U-iRO induction. Single cell RNA-seq further reveals the cell types in 2D and 3D organoids, 2D U-iRO dominated with mesenchyme and 3D U-iRO with tubule.
Project description:Kidney organoids are ideal models to study the complex process of human kidney development. Here we report the generation of functional kidney organoids by reprogramming human urine epithelial cells (hUCs). RNA-seq and ATAC-seq revealed the three-stage process of the 2D U-iRO induction. Single cell RNA-seq further reveals the cell types in 2D and 3D organoids, 2D U-iRO dominated with mesenchyme and 3D U-iRO with tubule.
Project description:Kidney organoids are ideal models to study the complex process of human kidney development. Here we report the generation of functional kidney organoids by reprogramming human urine epithelial cells (hUCs). RNA-seq and ATAC-seq revealed the three-stage process of the 2D U-iRO induction. Single cell RNA-seq further reveals the cell types in 2D and 3D organoids, 2D U-iRO dominated with mesenchyme and 3D U-iRO with tubule.
Project description:Kidney organoids are ideal models to study the complex process of human kidney development. Here we report the generation of functional kidney organoids by reprogramming human urine epithelial cells (hUCs). RNA-seq and ATAC-seq revealed the three-stage process of the 2D U-iRO induction. Single cell RNA-seq further reveals the cell types in 2D and 3D organoids, 2D U-iRO dominated with mesenchyme and 3D U-iRO with tubule.
Project description:Kidney diseases including acute kidney injury (AKI) and chronic kidney disease (CKD), which can progress to end stage renal disease (ESRD), are a worldwide health burden. Organ trans-plantation or kidney dialysis are the only effective available therapeutic tools. Therefore, in vitro models of kidney diseases and the development of prospective therapeutic means are highly demanded. Within the kidney, the glomeruli are involved in blood filtration and waste excre-tion, and are easily affected by changing cellular conditions. Puromycin aminonucleoside (PAN) is a nephrotoxin, which can be harnessed for imitating acute glomerular damage and modelling of glomerular disease. For this reason, we generated kidney organoids from three iPSC lines and treated these with PAN in order to induce kidney injury. Morphological observations re-vealed disruption of glomerular and tubular structures within the kidney organoids upon PAN treatment, which were confirmed by transcriptome analyses. Subsequent analyses revealed an upregulation of immune response as well as inflammatory and cell death-related processes. We concluded that treatment of iPSC-derived kidney organoids with PAN induces kidney injury mediated an intertwined network of inflammation, cytoskeletal re-arrangement, DNA damage, apoptosis and cell death. Furthermore, urine stem cell-derived kidney organoids can be used for modelling of kidney-associated diseases and drug discovery.
Project description:Kidney organoids are emerging as an increasingly applied model system to hold great promise for transplantation to individuals with end-stage renal disease and as a useful tool for kidney research. Multiple iPSC-derived renal organoids have been established to understand kidney development and disease. However, few disease models originated from adult renal tissue with fully mature cell fates have been set up to recapitulate kidney inflammation or fibrosis. Here we created a novel organoid model that faithfully representing the cellular state of inflammatory response during the progression of renal disease upon TNFα exposure. scRNA-seq showed signatured inflammatory chemokines, cytokines and inflammation-associated signaling pathways were activated in TNFα-treatment organoids together with injury-associated markers such as LCN2 and CLU. Donor age is associated with TNFα-induced inflammatory reaction in organoids. Kidney organoids from young donors showed more transcriptional changes by down-regulation of TGFβ and extracellular matrix genes. In summary, we established an in vitro TNFα-treated kidney organoid model that representing the cellular state of the inflammatory response during renal disease progression and provided a novel tool for studying inflammation-related kidney disease and drug discovery.