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Single-Cell Transcriptomics of Genome-Edited Kidney Organoids

ABSTRACT: Single-Cell Transcriptomics of Genome-Edited Kidney Organoids

PROVIDER: PRJNA559570 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR9943170_1.fastq.gz	Fastqsanger.gz
	SRR9943170_2.fastq.gz	Fastqsanger.gz
	SRR9943180_1.fastq.gz	Fastqsanger.gz
	SRR9943180_2.fastq.gz	Fastqsanger.gz
	SRR9943171_1.fastq.gz	Fastqsanger.gz

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Single-Cell Transcriptomics of Genome-Edited Kidney Organoids

Project description:We report the first use of genome-edited human kidney organoids, combined with single-cell transcriptomics, to study APOL1 risk variants at the native genomic locus in different nephron cell types. This approach captures interferon-mediated induction of APOL1 gene expression and cellular dedifferentiation with a secondary insult“second hit” of endoplasmic reticulum stress.

2020-01-24 | GSE135663 | GEO

Human pluripotent stem cell-derived kidney organoids reveal tubular epithelial pathobiology of heterozygous HNF1B-associated dysplastic kidney malformations CL

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.

2024-04-29 | E-MTAB-12824 | biostudies-arrayexpress

Human pluripotent stem cell-derived kidney organoids reveal tubular epithelial pathobiology of heterozygous HNF1B-associated dysplastic kidney malformations K

2024-04-29 | E-MTAB-12822 | biostudies-arrayexpress

Profiling <i>APOL1</i> Nephropathy Risk Variants in Genome-Edited Kidney Organoids with Single-Cell Transcriptomics.

Project description:BackgroundDNA variants in APOL1 associate with kidney disease, but the pathophysiologic mechanisms remain incompletely understood. Model organisms lack the APOL1 gene, limiting the degree to which disease states can be recapitulated. Here we present single-cell RNA sequencing (scRNA-seq) of genome-edited human kidney organoids as a platform for profiling effects of APOL1 risk variants in diverse nephron cell types.MethodsWe performed footprint-free CRISPR-Cas9 genome editing of human induced pluripotent stem cells (iPSCs) to knock in APOL1 high-risk G1 variants at the native genomic locus. iPSCs were differentiated into kidney organoids, treated with vehicle, IFN-γ, or the combination of IFN-γ and tunicamycin, and analyzed with scRNA-seq to profile cell-specific changes in differential gene expression patterns, compared with isogenic G0 controls.ResultsBoth G0 and G1 iPSCs differentiated into kidney organoids containing nephron-like structures with glomerular epithelial cells, proximal tubules, distal tubules, and endothelial cells. Organoids expressed detectable APOL1 only after exposure to IFN-γ. scRNA-seq revealed cell type-specific differences in G1 organoid response to APOL1 induction. Additional stress of tunicamycin exposure led to increased glomerular epithelial cell dedifferentiation in G1 organoids.ConclusionsSingle-cell transcriptomic profiling of human genome-edited kidney organoids expressing APOL1 risk variants provides a novel platform for studying the pathophysiology of APOL1-mediated kidney disease.

| S-EPMC7351353 | biostudies-literature

Distalised kidney organoids

Project description:Distalised kidney organoids

| PRJNA765442 | ENA

scRNAseq of heterozygous HNF1B-mutant vs non-mutant kidney organoids derived from human embryonic stem cells

Project description:Human embryonic stem cell (hESC) line Man-13 was edited by CRISPR resulting in a hESC line carrying a heterozygous frameshift mutation with a premature stop codon in exon-1 of the HNF1B gene ([p.Val61Argfs*18]), functionally equivalent to a heterozygous whole-gene deletion. Kidney organoids were then created by differentiation (as per Takasato et al, 2015; Bantounas et al, 2018; Bantounas et al 2021) of this line and an isogenic non-mutant control line. Single-cell RNAseq (scRNAseq) was then performed on day-25 of differentiation to identify transcriptomic differences, as well as differences in identity and numbers of the cell populations comprising the organoids, with the aim of mechanistically explaining developmental aberrations observed in patients with mutations in this gene.

2024-04-30 | E-MTAB-13500 | biostudies-arrayexpress

SINGLE CELL ANALYSIS OF POLYCYSTIC KIDNEY DISEASE USING HUMAN PLURIPOTENT STEM CELL- DERIVED KIDNEY ORGANOIDS

Project description:To reveal the key pathways involved in kidney cystogenesis. We performed single nuclei gene expression and ATAC profiling using kidney organoids from ARPKD patients-iPSCs derived organoids.

2023-10-09 | GSE244608 | GEO

Single-cell RNA-seq of engineered healthy human kidney organoids

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.

2020-04-05 | GSE147863 | GEO

The immunogenicity of human kidney organoids

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.

2022-08-25 | GSE211803 | GEO

Single-cell RNA-seq of human kidney organoids

Project description:We used scRNA-Seq (and other biological experiments) to study the impact of a high oscillatory glucose regime in the differentiation and metabolic status of human kidney organoids further emulating early hallmarks of the diabetic kidney. To study the interplay between those changes and SARS-CoV-2 infection we assessed the effect of early stages of infection (1 day post infection) in normoglicemic (5 mM), hyperglicemic (5-25 mM oscillatory regime) and differentiating (11 mM) conditions. We retrieved metabolic changes and an upregulation of inflammatory related processes upon infection, whilst there was not an impact in the viability of the different cell types in the kidney organoids. Also, we studied the differences between ACE2 CRISPR/Cas9 knockouts and ACE2 WT organoids, using single cell RNA sequencing to resolve cell-type specific and cell proportion changes.

2022-05-12 | GSE181002 | GEO

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