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Status |
Public on Mar 04, 2022 |
Title |
The nephrotxin Puromycin aminonucleoside induces injury in kidney organoids differentiated from human urine SIX2-positive stem cell derived induced pluripotent stem cells. |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by array
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Summary |
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.
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Overall design |
The transcriptomes of iPSC-derived spheroids and kidney organoids with and without Puromycin aminonucleoside (PAN) treatment were compared by microarray analysis (PrimeView Human Gene Expression Array, Affymetrix, Thermo Fisher Scientific).
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Contributor(s) |
Wasco W, Lisa N, James A |
Citation(s) |
35203286 |
Submission date |
Oct 29, 2021 |
Last update date |
Mar 05, 2022 |
Contact name |
Wasco Wruck |
E-mail(s) |
wasco.wruck@med.uni-duesseldorf.de
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Organization name |
Universitätsklinikum Düsseldorf
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Street address |
Moorenstr. 5
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City |
Düsseldorf |
ZIP/Postal code |
40225 |
Country |
Germany |
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Platforms (1) |
GPL23159 |
[Clariom_S_Human] Affymetrix Clariom S Assay, Human (Includes Pico Assay) |
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Samples (6)
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GSM5661634 |
kidney organoids control [UMK1_con_1] |
GSM5661635 |
kidney organoids control [UMK1_con_2] |
GSM5661636 |
PAN treated kidney organoids [UMK1_PAN_1] |
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Relations |
BioProject |
PRJNA776246 |
Supplementary file |
Size |
Download |
File type/resource |
GSE186823_RAW.tar |
7.3 Mb |
(http)(custom) |
TAR (of CEL) |
Processed data included within Sample table |
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