An integrated organoid omics map extends modeling potential of kidney disease
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE213972 | GEO | 2023/05/23
REPOSITORIES: GEO
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Project description:Kidney organoids are a promising model to study kidney disease, but their use is constrained by limited knowledge of their functional protein expression profile. Here, we define the organoid proteome and transcriptome trajectories over culture duration and upon exposure to TNFα, a cytokine stressor. Older organoids increase deposition of extracellular matrix but decrease expression of glomerular proteins. Single cell transcriptome integration reveals that most proteome changes localize to podocytes, tubular and stromal cells. TNFα treatment of organoids results in 322 differentially expressed proteins, including cytokines and complement components. Transcript expression of these 322 proteins is significantly higher in individuals with poorer clinical outcomes in proteinuric kidney disease. Key TNFα-associated protein (C3 and VCAM1) expression is increased in both human tubular and organoid kidney cell populations, highlighting the potential for organoids to advance biomarker development. By integrating kidney organoid omic layers, incorporating a disease-relevant cytokine stressor and comparing with human data, we provide crucial evidence for the functional relevance of the kidney organoid model to human kidney disease.
| S-EPMC10425428 | biostudies-literature
Project description:An integrated organoid omics map extends modeling potential of kidney disease
| PRJNA883395 | ENA
Project description:Kidney organoids are a valuable and innovative model to understand genetic diseases, kidney development and transcriptomic dynamics. However, their proteome has not been analyzed so far. Here, we analyzed the organoid proteome after treatment of organoids with 5ng/mL TNFalpha for 24h and 48h compared with vehicle control (VC). Incubation of organoids (day 25 of differentiation) with TNFalpha led to an activation of NFkappaB signaling, and, interestingly, secretion of cytokines and complement components, alongside with extracellular matrix components. Interestingly, this signaling system directly links inflammatory signaling, production of cytokines and complement; and production of extracellular matrix. Thus, we provide a repository of kidney organoid proteins that revealed the potential to model pathophysiological pathways beyond genetic diseases. Organoids were grown according to the Freedman protocol (Freedman, Brooks et al. 2015, Czerniecki, Cruz et al. 2018). The IPSCs were differentiated for a three-week period until first spheroids from. We started TNFa stimulation at day 25, with the 24h stimulation ending on day 26 and the 48h stimulation ending on day 27. We chose day 25 because it lies centrally in the day 21 to day 29 window, where we observe reproducible spheroids with limited off-target differentiation of organoids, which becomes an issue after day 29.
2023-05-12 | PXD029696 | Pride
Project description:Kidney organoids are a valuable and innovative model to understand genetic diseases, kidney development and transcriptomic dynamics. However, their proteome has not been analyzed so far. Here, we analyzed the organoid proteome after treatment of organoids with 5ng/mL TNFalpha for 24h and 48h compared with vehicle control (VC). Incubation of organoids (day 25 of differentiation) with TNFalpha led to an activation of NFkappaB signaling, and, interestingly, secretion of cytokines and complement components, alongside with extracellular matrix components. Interestingly, this signaling system directly links inflammatory signaling, production of cytokines and complement; and production of extracellular matrix. Thus, we provide a repository of kidney organoid proteins that revealed the potential to model pathophysiological pathways beyond genetic diseases. Organoids were grown according to the Freedman protocol (Freedman, Brooks et al. 2015, Czerniecki, Cruz et al. 2018). The IPSCs were differentiated for a three-week period until first spheroids from. We started TNFa stimulation at day 25, with the 24h stimulation ending on day 26 and the 48h stimulation ending on day 27. We chose day 25 because it lies centrally in the day 21 to day 29 window, where we observe reproducible spheroids with limited off-target differentiation of organoids, which becomes an issue after day 29.
2023-05-12 | PXD029718 | Pride
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2018-12-13 | GSE111360 | GEO
Project description:Transcriptomic profiles of 6 commercially-available human patient-derived gastrointestinal organoid lines were obtained and compared to transcriptomic profile of a commercially available human iPSC-induced colon organoid line. Transcriptomic profile of iPSC-derived human colon organoid line was compared after culture in either Corning growth-factor-reduced Matrigel (Corning 356231) or MilliporeSigma growth-factor-reduced ECMGel (E6909)
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Project description:In order to provide multi-omic resolution to human retinal organoid developmental dynamics, we performed scRNA-seq and scATAC-seq from the same cell suspension across a time course (6-46 weeks) of human retinal organoid development. This data set covers all the retinal organoid scRNA-seq data generated from IMR90 and409B2-iCas9 cell lines.
2023-03-12 | E-MTAB-12715 | biostudies-arrayexpress
Project description:To identify downstream genes involved in cholangiocarcinoma development by genetic manipulations of Kras, TGFbR2, and CDH1, we cultured the biliary organoid from the extrahepatic bile duct of Cre-negative LSL-KrasG12D;Tgfbr2flox/flox;CDH1flox/flox (KTC) mice, and induced gene recombination using a lentivirus expressing Cre-recombinase (Cre+ KTC organoid) or control lentivirus (Cre- KTC organoid). Then, we compared gene expression signatures between Cre- KTC organoid organoid and Cre+ KTC organoid.
2017-04-30 | GSE88900 | GEO