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Human Pluripotent Stem Cell-Derived Kidney Organoids for Modeling Epithelial Transport and Injury

ABSTRACT: Human Pluripotent Stem Cell-Derived Kidney Organoids for Modeling Epithelial Transport and Injury

PROVIDER: PRJNA542638 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR9047573_1.fastq.gz	Fastqsanger.gz
	SRR9047573_2.fastq.gz	Fastqsanger.gz
	SRR9047574_1.fastq.gz	Fastqsanger.gz
	SRR9047574_2.fastq.gz	Fastqsanger.gz

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Human Pluripotent Stem Cell-Derived Kidney Organoids for Modeling Epithelial Transport and Injury

Project description:Maximizing the potential of human kidney organoids for drug testing, regenerative medicine and to model development and disease requires addressing cell immaturity, the lack of a branching collecting system and the off target cell types. Here we establish methods to independently generate the two kidney progenitor cell populations – metanephric mesenchyme and ureteric bud. Combining these two progenitor cell types results in organoids with an improved branched collecting system. We also identified the hormones aldosterone and arginine vasopressin as critical to promote maturation of collecting duct cell types. The resulting organoids contain the full range of epithelial cells in the nephron, including principal and intercalated cells. By scRNA-seq, we demonstrate superior proximal tubule maturation and reduced off-target cell populations using this protocol.

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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.

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

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