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:This study used snATAC-seq to profile Chromatin accessibility in 26 day-old iPSC-derived kidney organoids, treated with TGFB1, the EzH2 inhibitor GSK343, a combination of both or a vehicle control for 48 hours (days 24-26) before harvesting. 2 organoids per condition were pooled and dissociated using a cold-active protease. Nuclei were extracted and profiled using the 10X Genomics Single-cell ATAC reagent kit v1.1. Libraries were sequenced using paired-end reads on an Illumina NovaSeq 6000. Initial processing was performed using CellRanger ATAC v1.2.0 (10X Genomics).
Project description:Bulk ATAC-seq was performed on human, chimpanzee, bonobo, and macaque stem cell-derived cerebral organoids. ATAC-seq was performed on day 60 (2 months old) and day 120 (4 months old) cerebral organoids.
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.