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Human iPSC-derived glomeruli provide an advanced model to interrogate podocyte biology and accurately recapitulate podocytopathy

ABSTRACT: Human iPSC-derived glomeruli provide an advanced model to interrogate podocyte biology and accurately recapitulate podocytopathy

PROVIDER: PRJNA438893 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR6854630_1.fastq.gz	Fastqsanger.gz
	SRR6854630_2.fastq.gz	Fastqsanger.gz
	SRR6854631_1.fastq.gz	Fastqsanger.gz
	SRR6854631_2.fastq.gz	Fastqsanger.gz
	SRR6854622_1.fastq.gz	Fastqsanger.gz

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Human iPSC-derived glomeruli provide an advanced model to interrogate podocyte biology and accurately recapitulate podocytopathy

Project description:Podocytes are highly specialised cells within the glomeruli of the kidney that maintain the filtration barrier by forming interdigitating foot processes and slit-diaphragms. Disruption to these features result in proteinuria and glomerulosclerosis. Studies into podocyte biology and disease have previously relied on conditionally immortalised cell lines due to the non- proliferative nature of this cell type. Here we describe an advanced model to study both podocyte and glomerular biology using isolated glomeruli from kidney organoids derived from human pluripotent stem cells.

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Project description:We identified Fox1 and Foxc2 core transcription factors in kidney glomeruli. To investigate their transcriptional regulatory roles in glomeruli, we performed ChIPseq of Foxc1 and Foxc2 in adult mouse kidney glomeruli. The genome wide distribution of Foxc1/2 binding sites revealed they regulated the differentiation and mature state of adult podocyte to maintain kidney homeostatis.

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Project description:The goal of this study was to identify transcriptomic changes of mouse glomeruli in mice with podocyte-specific deletion of Kruppel-like factor 4, a zinc-finger transcription factor.

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Transcriptomic analysis of glomeruli following podocyte-loss of Klf4

Project description:Transcriptomic analysis of glomeruli following podocyte-loss of Klf4

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Comparison of Glomerular and Podocyte mRNA Profiles in eNOS-/- Diabetic Mice Induced by Streptozotocin

Project description:We compared mRNA profiles of isolated glomeruli versus sorted podocytes between diabetic and control mice. IRG mice crossed with eNOS-/- mice were further bred with podocin-rTTA and TetON-Cre mice to permanently label podocytes before the diabetic injury. Diabetes was induced by injection of streptozotocin. mRNA profiles of isolated glomeruli and sorted podocytes from diabetic and control mice at 10 weeks after induction of diabetes were examined. Consistent with the previous reports, expression of podocyte-specific markers in the glomeruli were down-regulated in the diabetic mice compared to controls. However, these differences disappeared when mRNA levels were corrected for podocyte number per glomerulus. Interestingly, the expression of these markers was not altered in sorted podocytes from diabetic mice, suggesting that the reduced expression of podocyte markers in isolated glomeruli is likely a secondary effect of reduced podocyte number, rather than the loss of differentiation markers. Analysis of the differentially expressed genes in diabetic mice also revealed distinct up-regulated pathways in the glomeruli (mitochondrial function and oxidative stress) and podocytes (actin organization). In conclusion, our data suggest that podocyte-specific gene expression in transcriptome obtained from the whole glomeruli may not represent those of podocytes in the diabetic kidney. We compared mRNA profiles of isolated glomeruli versus sorted podocytes between diabetic and control mice.

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Core TF Foxc1/2 reinforce differentiation of adult podocyte in glomeruli

Project description:Core TF Foxc1/2 reinforce differentiation of adult podocyte in glomeruli

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