Project description:Safety issues of human iPSC-derived kidney organoids as a regenerative therapy need to be evaluated. Therefore, we studied the immunogenicity of human iPSC-derived kidney organoids. We subcutaneously implanted kidney organoids in immune-deficient IL2Ry-/-RAG2-/- mice for 1 month and hereafter performed adoptive transfer of healthy allogeneic human PBMC. We used single cell RNA sequencing (scRNA-seq) to analyze the diversity of kidney organoid cells and immune cell profiles. We investigated whether innate and adaptive immune cells invade kidney organoids, evoke an immune response, and influence the kidney organoid differentiation and functional capacity. Understanding the immunogenicity of kidney organoids will advance studies in the applicability of kidney organoids for regenerative medicine. Furthermore, it can serve as an in-vivo transplantation model to study solid organ transplantation.
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:Hepatocyte nuclear factor 1B (HNF1B) encodes a transcription factor expressed in developing human kidney epithelia. Heterozygous HNF1B mutations are the commonest monogenic cause of dysplastic kidney malformations (DKMs). To understand their pathobiology, we generated heterozygous HNF1B mutant kidney organoids from CRISPR-Cas9 gene-edited human ESCs and iPSCs reprogrammed from a family with HNF1B-asscociated DKMs. Mutant organoids contained enlarged malformed tubules and displayed deregulated cell turnover. This submission is RNAseq of organoids from MAN13 embryonic stem cells.
Project description:Hepatocyte nuclear factor 1B (HNF1B) encodes a transcription factor expressed in developing human kidney epithelia. Heterozygous HNF1B mutations are the commonest monogenic cause of dysplastic kidney malformations (DKMs). To understand their pathobiology, we generated heterozygous HNF1B mutant kidney organoids from CRISPR-Cas9 gene-edited human ESCs and iPSCs reprogrammed from a family with HNF1B-asscociated DKMs. Mutant organoids contained enlarged malformed tubules and displayed deregulated cell turnover. This submission contains kidney tissue samples.
Project description:Single-cell RNA-seq of engineered healthy human kidney organoids. These data are part of a larger investigation (data not provided here) showing that SARS-CoV-2 can directly infect engineered human blood vessel organoids and human kidney organoids which can be inhibited by human recombinant soluble ACE2 (hrsACE2), demonstrating that hrsACE2 can significantly block early stages of SARS-CoV-2 infections.
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.