In vivo developmental trajectories of human podocyte development inform in vitro differentiation of pluripotent stem-cell derived podocytes
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE124392 | GEO | 2019/06/19
REPOSITORIES: GEO
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Project description:Podocytes play an important filtration role in the kidney. We examined culture condition for efficient podocyte induction and established a method to selectively induce podocytes from human iPS cells. To understand how expression profiles of human iPS cell-derived podocytes were close to that in vivo, we isolated human adult podocytes for human adult kidney. Purified RNAs from human iPS cells, nephron progenitor cells, human immortalized podocyte cell line, human iPS cell-derived podocytes, and sorted human adult podocytes were analyzed by RNA-seq.
2019-01-15 | GSE116471 | GEO
Project description:In vivo developmental trajectories of human podocyte development inform in vitro differentiation of pluripotent stem-cell derived podocytes
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Project description:We identified binding sites of the Wilms' tumor suppressor protein WT1 in the mouse podocyte genome in vivo by ChIP-seq. Furthermore, we provide a podocyte transcriptome derived from primary podocytes that were isolated by FACS on mouse glomeruli. In short, we show that WT1 activates a highly specific podocyte transcriptome by binding to putative podocyte-specific enhancers and TSS of target genes. Genes bound by WT1 in podocytes include the majority of genes mutated in hereditary podocytopathies as well as components of the slit diaphragm, actin cytoskeleton, extracellular matrix, and within endocytosis pathways. Furthermore, we infer a podocyte TF network from DNA-binding motifs enriched at WT1-bound loci that includes Tead, Lmx1b, Mafb, Tcf21, and Fox-class transcription factors. Examination of transcription factor binding sites for WT1 by ChIP-seq. Transcriptome analysis of podocytes by RNA-seq.
2014-12-11 | E-GEOD-64063 | biostudies-arrayexpress
Project description:Transcriptomes of differentiated cells of the conditionally immortalized mouse podocyte cell line SVI (Schiwek et al., Kidney Int. 66: 91-101, 2004) were determined as described in Kabgani et al. (PLoS One 7:e34907, 2012). The transcriptomes of the podocyte cell line were mapped on a protein-protein interaction network of the podocyte (PodNet). Together with other transcriptomes taken from GEO, we analyzed differential gene regulation and differential regulation of protein-protein interactions between cultured podocytes and differentiated in vivo podocytes. Three independent batches were used.
2012-10-16 | E-GEOD-41523 | biostudies-arrayexpress
Project description:Podocytes form filtration barrier through foot process around glomerualar basement membrane and selectively permit permeability of molecular smaller than albumin. Diabetes can cause podocyte pathological changes leading to high urine albumin level. Diabetic mouse model OVE26 has extremly high urine albumin and previously studies indicated its podocyte damaged. Here we try to find the key genes change in OVE26 diabetic mouse model podocyte by microarray assay while normal FVB mouse podocyte set as control. Podocyte eGFP transgenic mice were made on FVB background and crossbred to OVE26 diabetic model. Glomeruli isolated from OVE-GFP mice were digested by trypsin into signal cell. Podocytes with GFP were sorting out by FACS.
2012-03-02 | E-GEOD-36209 | biostudies-arrayexpress
Project description:Alport syndrome (AS) is a genetic defect involving mutations of collagen IV α3, α4 or α5 genes, resulting in distinctive clinical features: kidney disease, hearing loss and eye abnormalities. Podocytes are responsible of production and correct assembly of the collagen IV isoforms, however, specific alterations of podocyte phenotype are currently scarce. We here generated immortalised AS urine-derived podocyte from three different patients. AS podocytes expressed a typical podocyte signature when compared to normal urine-derived podocytes, with comparable expression of podocyte markers. Each AS cell line showed a collagen IV profile that reflected the typical patient mutation. Furthermore, by RNA-sequencing 348 genes were found differentially expressed in Alport podocytes. Gene Ontology analysis underlined enrichment in genes involved in cell motility, adhesion, survival and angiogenesis. In parallel, AS podocyte motility was reduced. In conclusion, our data clearly indicate that AS podocytes display altered features connected but distinct from the collagen alterations.
2020-06-18 | GSE134011 | GEO
Project description:The progression of proteinuric kidney disease is associated with podocyte loss but the mechanisms remain unclear. Podocytes reenter the cell cycle to repair damaged ds DNA breaks. However, unsuccessful repair results in podocytes crossing the G1/S checkpoint and undergoes abortive cytokinesis. In this study, we identified Pfn1 as a major contributor in maintaining glomerular integrity and its loss in mice results in severe proteinuria, and kidney failure due to podocyte mitotic catastrophe, characterized by abundant multinucleated cells. Reentry of podocytes were identified by using FUCCI-2aR mice, accompanying the alteration of cell-cycle associated proteins, such as P21, P53, Cyclin B, and Cyclin D. Podocyte-specific translating ribosome affinity purification (TRAP) and RNAseq revealed a reduction of Ribosomal RNA-processing protein 8 (Rrp8) and re-expression of Rrp8 partially rescued the in-vitro phenotype. Clinical analysis of patients with proteinuric kidney disease demonstrated multinucleated podocytes and reduced podocyte profilin1 in kidney tissue. These results suggest that profilin is indispensible in regulating podocyte cell cycle and its disruption contributes to podocyte loss through mitotic catastrophe.
2023-12-01 | GSE227414 | GEO
Project description:Podocyte injury is involved in the onset and progression of various kidney diseases. We previously demonstrated that the transcription factor, old astrocyte specifically induced substance (OASIS) in myofibroblasts, contributes to kidney fibrosis, as a novel role of OASIS in the kidneys. Importantly, we found that OASIS is also expressed in podocytes; however, the pathophysiological significance of OASIS in podocytes remains unknown. Upon lipopolysaccharide (LPS) treatment, there is an increase in OASIS in murine podocytes. Enhanced serum creatinine levels and tubular injury, but not albuminuria and podocyte injury, are attenuated upon podocyte-restricted OASIS knockout in LPS-treated mice, as well as diabetic mice. The protective effects of podocyte-specific OASIS deficiency on tubular injury are mediated by protein kinase C iota (PRKCI/PKCι), which is negatively regulated by OASIS in podocytes. Furthermore, podocyte-restricted OASIS transgenic mice show tubular injury and tubulointerstitial fibrosis, with severe albuminuria and podocyte degeneration. Finally, there is an increase in OASIS-positive podocytes in the glomeruli of patients with minimal change nephrotic syndrome and diabetic nephropathy. Taken together, OASIS in podocytes contributes to podocyte and/or tubular injury, in part through decreased PRKCI. The induction of OASIS in podocytes is a critical event for the disturbance of kidney homeostasis.
2022-06-22 | GSE206525 | GEO
Project description:Podocyte effacement and loss characterizes glomerulopathies such as diabetic nephropathy, lupus, and glomerular toxicity. Human primary podocyte-like epithelial cells cultured from urine (ECU) were characterized as a window to understand podocyte regeneration in these glomerulopathies. Cytokines TNF, and VEGF stimulated regrowth, whereas FGF-1 and IL1 inhibited growth, consistent with other podocyte or parietal epithelial cell models. Review of published micrographs indicated that podocyte foot processes in rodent kidneys interdigitated exclusively with foot processes from other cells, suggesting podocytes practice self-avoidance. In culture, ECU avoided close interactions with other cells arising from the same clone, until enough cells grew for the culture to become confluent. In contrast, ECU derived from multiple clones associated actively to form contiguous monolayers. Gene expression profiling of eight clonal ECU colonies using RNA sequencing revealed that each colony expressed a highly variable profile of the 53 Protocadherin genes. Variable combinations of the 53 Protocadherin PCDHA-, PCDHB-, and PCDHG- gene products are known to act homophilically to direct self-avoidance interactions in human neurons, so PCDH- genes are postulated to govern self-avoidance similarly in podocytes. Such protocadherin profiles could be considered cell names. Transcriptional profiles of ECUs suggest they may represent intermediate stages of Parietal Epithelial Cells (PECs) differentiating into podocytes. They further suggest that each podocyte practices self-avoidance, interdigitating selectively with other cells in the glomerulus. To enable further investigation of multi-clonal podocyte interactions, five podocyte clones were immortalized using temperature-sensitive SV40 Large T antigen. These results suggest that non-self interdigitation of new podocytes with remnant podocytes may facilitate replacement of dying podocytes and re-establishment of a functional filtration barrier.
2024-02-24 | GSE226224 | GEO
Project description:The specialized glomerular epithelial cell (podocyte) of the kidney is a complex cell that is often damaged in glomerular diseases. Study of this cell type is facilitated by an in vitro system of propagation of conditionally immortalized podocytes. Here, genes that are differentially expressed in this in vitro model of podocyte differentiation are evaluated. Conditionally immortalized undifferentiated mouse podocytes were cultured under permissive conditions at 33*C. Podocytes that were differentiated at the non-permissive conditions at 37*C were used for comparison.
2010-08-28 | E-GEOD-23856 | biostudies-arrayexpress