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The nephrotxin Puromycin aminonucleoside induces injury in kidney organoids differentiated from human urine SIX2-positive stem cell derived induced pluripotent stem cells.

ABSTRACT: The nephrotxin Puromycin aminonucleoside induces injury in kidney organoids differentiated from human urine SIX2-positive stem cell derived induced pluripotent stem cells.

PROVIDER: PRJNA776246 | ENA |

REPOSITORIES: ENA

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The nephrotxin Puromycin aminonucleoside induces injury in kidney organoids differentiated from human urine SIX2-positive stem cell derived induced pluripotent stem cells.

Project description:Kidney diseases including acute kidney injury (AKI) and chronic kidney disease (CKD), which can progress to end stage renal disease (ESRD), are a worldwide health burden. Organ trans-plantation or kidney dialysis are the only effective available therapeutic tools. Therefore, in vitro models of kidney diseases and the development of prospective therapeutic means are highly demanded. Within the kidney, the glomeruli are involved in blood filtration and waste excre-tion, and are easily affected by changing cellular conditions. Puromycin aminonucleoside (PAN) is a nephrotoxin, which can be harnessed for imitating acute glomerular damage and modelling of glomerular disease. For this reason, we generated kidney organoids from three iPSC lines and treated these with PAN in order to induce kidney injury. Morphological observations re-vealed disruption of glomerular and tubular structures within the kidney organoids upon PAN treatment, which were confirmed by transcriptome analyses. Subsequent analyses revealed an upregulation of immune response as well as inflammatory and cell death-related processes. We concluded that treatment of iPSC-derived kidney organoids with PAN induces kidney injury mediated an intertwined network of inflammation, cytoskeletal re-arrangement, DNA damage, apoptosis and cell death. Furthermore, urine stem cell-derived kidney organoids can be used for modelling of kidney-associated diseases and drug discovery.

2022-03-04 | GSE186823 | GEO

Gene expression profiling of Six2-positive nephron progenitors from mouse embryo

Project description:Nephron progenitors in the embryonic kidney propagate while generating differentiated nephrons. However, the progenitors in mice terminally differentiate shortly after birth. We defined culture conditions to selectively propagated nephron progenitors in vitro in an undifferentiated state. To understand how expression profiles of Six2+ cells changed during culture in vitro compared with in vivo, we performed microarray analysis of Six2+ cells at E11.5 (starting material) and P0 (experiencing 8 days in vivo), and cultured Six2+ cells at E11.5 for 8 days or 19 days. Microarray analysis were performed with isolated Six2-positive nephron progenitors from transgenic mice embryo at E11.5 or P0, and cultured E11.5 Six2+ cells for 8 or 19 days in conditioned media. P0 non-progenitors represent Six2-GFP-negative cells at P0.

2016-04-14 | E-GEOD-79024 | biostudies-arrayexpress

Effect of 30Kc19α-Lin28A protein on gene expression in osteogenesis of urine-derived stem cells

Project description:To elucidate the function of 30Kc19α-Lin28A protein in osteogenic differentiation of urine-derived stem cells, we established urine-derived stem cell lines differentiated with or without protein treatment. We then performed gene expression profiling analysis using data obtained from RNA-seq of osteogenic differentiated urine-derived stem cells with or without 30Kc19α-Lin28A protein treatment, undifferentiated urine-derived stem cells, and human osteoblasts

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Gene expression profiling of Six2-positive nephron progenitors from mouse embryo

2016-04-14 | GSE79024 | GEO

RNA-seq Analysis in 4T07 Control (4T07-CTL) and Six2 Overexpression (4T07-Six2) cells

Project description:To determine the molecular mechanisms by which Six2 regulates metastatic colonization, we performed RNA-seq analysis on murine triple-negative 4T07 Control (4T07-CTL) and Six2 overexpressing (4T07-Six2) cells. Using both targeted and unbiased gene signature analyses, we found that Six2 differentially regulates gene signatures associated with stemness. Additionally, we confirmed that in several triple-negative breast cancer (TNBC) models, Six2 enhanced the expression of genes (identified as among the highest upregulated genes in response to Six2 overexpression) associated with embryonic stem cell programs. When combined with our in vitro and in vivo stemness-associated phenotypic assays, these data suggest that Six2 may play a similar role in mediating stemness characteristics during tumor progression as it does during development, and that this role may allow it to mediate late-stage metastasis by enhancing the ability of cells to self-renew and survive at secondary sites.

2020-01-30 | GSE123489 | GEO

Genome-wide maps of Six2 and b-catenin in mesenchymal nephron progenitors

Project description:Self-renewing undifferentiated nephron progenitors express Six2, a transcription factor that is required for their maintenance as undifferentiated progenitors. Differentiation of nephron progenitors is triggered by Wnt/b-catenin signaling. In order to understand how Six2 and Wnt signaling counteract each other, we performed ChIP-seq of Six2 and b-catenin in mesenchymal nephron progenitor cells. Nephron progenitors were FACS-isolated from BAC transgenic Six2GFPcre-positive embryonic kidneys at E16.5. For Six2 ChIP, freshly FACS isolated Six2+ cells were used. For b-catenin ChIP, FACS isolated Six2+ cells were aggregated by centrifugation at 850g for 5min and incubated in 10%FBS/DMEM containing 4uM BIO for 24hrs.

2012-09-11 | E-GEOD-39837 | biostudies-arrayexpress

Generation of induced neural stem cells from urine derived cells by synthetic mRNA

Project description:Analysis of induced neural stem cells from urine derived cells by synthetic mRNA vs. H9 embryonic stem cell derived neural stem cells and urine derived cells. Results provide insight into molecular similarities between induced neural stem cells and H9 embryonic stem cells derived neural stem cells.

2019-02-03 | GSE119669 | GEO

Bulk RNA Sequencing Analysis on the Effects of SIX2 Knock Down on Stem Cell Derived Beta cells.

Project description:We reveal that SIX2 regulates important transcriptomic aspects of stem cell derived beta cells

2020-05-26 | GSE147737 | GEO

The miRNA expression of exosome secreted by human urine-derived stem cells

Project description:We identify miRNA profiles from exosomes of human urine-derived stem cells (USCs).

2022-06-18 | GSE206162 | GEO

Generation of induced keratinocyte stem cells from human urine cells by defined transcription factors

Project description:Analysis of induced keratinocyte stem cells from male/female urine cells (MiKSC/FiKSC) by defined transcription factors vs. foreskin derived primary human neonatal epidermal keratinocytes (pKC) and male/female urine cells (MUC/FUC). Results provide insight into molecular similarities between induced keratinocyte stem cells and human foreskin derived primary human neonatal epidermal keratinocytes.

2019-04-11 | GSE129316 | GEO

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