GEO accession GSE297954 is currently private and is scheduled to be released on May 05, 2026.
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ABSTRACT:
PROVIDER: PRJNA1267027 | ENA |
REPOSITORIES: ENA
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Project description:Recreating pathophysiology of CLN2 disease and demonstrating reversion by TPP1 gene therapy in hiPSCs-derived retinal organoid and retina-on-chip
| PRJNA1022020 | ENA
Project description:Mutations in tripeptidyl peptidase 1 (TPP1) gene lead to late infantile neuronal ceroid lipofuscinosis CLN2, characterized by lysosomal accumulation of lipofuscins predominantly found in brain and retina. The ocular phenotype is characterized by bilateral outer retinal degeneration that leads to complete vision loss. CLN2 animal models struggle in recapitulating the retinal phenotype observed in patients. Here, we leveraged human induced pluripotent stem cell (hiPSC)-derived retinal organoids (ROs), retinal pigmented epithelial (RPE) cells, and retina-on-chip (RoC) technologies to model CLN2 disease in vitro in patient-specific microphysiological models of the human retina. Using these models, we were able to recreate the major clinical histological hallmark of CLN2 patients, namely the accumulation of lipofuscins containing subunit C of mitochondrial ATP synthase (SCMAS) and lipids mainly in the outer retina. Furthermore, single-cell RNA-sequencing of CLN2 ROs revealed a dysregulation of translational and mitochondrial function in cones. Finally, we demonstrate that an adeno-associated virus (AAV)-mediated TPP1 gene therapy was able to restore TPP1 expression and could decrease and even prevent SCMAS accumulations. In summary, our study produced novel human-relevant microphysiological retinal disease models, uncovered new mechanisms of CLN2 pathophysiology in the human retina, and demonstrated the immense potential of AAV9.hCLN2 gene therapy for CLN2 disease potentially treating and even curing blindness of affected individuals.
2025-07-31 | GSE244262 | GEO
Project description:Mutations in tripeptidyl peptidase 1 (TPP1) gene lead to late infantile neuronal ceroid lipofuscinosis CLN2, characterized by lysosomal accumulation of lipofuscins predominantly found in brain and retina. The ocular phenotype is characterized by bilateral outer retinal degeneration that leads to complete vision loss. CLN2 animal models struggle in recapitulating the retinal phenotype observed in patients. Here, we leveraged human induced pluripotent stem cell (hiPSC)-derived retinal organoids (ROs), retinal pigmented epithelial (RPE) cells, and retina-on-chip (RoC) technologies to model CLN2 disease in vitro in patient-specific microphysiological models of the human retina. Using these models, we were able to recreate the major clinical histological hallmark of CLN2 patients, namely the accumulation of lipofuscins containing subunit C of mitochondrial ATP synthase (SCMAS) and lipids mainly in the outer retina. Furthermore, single-cell RNA-sequencing of CLN2 ROs revealed a dysregulation of translational and mitochondrial function in cones. Finally, we demonstrate that an adeno-associated virus (AAV)-mediated TPP1 gene therapy was able to restore TPP1 expression and could decrease and even prevent SCMAS accumulations. In summary, our study produced novel human-relevant microphysiological retinal disease models, uncovered new mechanisms of CLN2 pathophysiology in the human retina, and demonstrated the immense potential of AAV9.hCLN2 gene therapy for CLN2 disease potentially treating and even curing blindness of affected individuals.
2025-07-25 | GSE297954 | GEO
Project description:Human neuromuscular organoids (NMOs) hold a great potential to study the pathophysiology of functional human skeletal muscle in vitro due to the presence of both muscular and neuronal compartments organized in a their three-dimensional (3D) context and to be derived from induced pluripotent stem cells (hiPSCs).
2025-05-30 | GSE226477 | GEO
Project description:Reversion of Alzheimer’s disease signatures
| PRJNA564801 | ENA
Project description:In our study, PRDM14 and NFRkB were found to enhance the reprogramming of human fibroblasts to hiPSCs in the presence of OCT4, SOX2, KLF4, with/without c-MYC (OSK/OSKC). To examnie if the obtained hiPSC share similar expression signature with hESC, we conducted the microarray analysis on the hiPSCs, hESCs and fibroblasts. The result showed that all of the examined hiPSCs resembled hESCs, but differed from fibroblasts MRC5. 4 hiPSC lines, 2 hESC lines and 1 type of fibroblasts were analyzed in total. Each sample is done in duplicates.
2010-10-20 | E-GEOD-22792 | biostudies-arrayexpress
Project description:In our study, PRDM14 and NFRkB were found to enhance the reprogramming of human fibroblasts to hiPSCs in the presence of OCT4, SOX2, KLF4, with/without c-MYC (OSK/OSKC). To examnie if the obtained hiPSC share similar expression signature with hESC, we conducted the microarray analysis on the hiPSCs, hESCs and fibroblasts. The result showed that all of the examined hiPSCs resembled hESCs, but differed from fibroblasts MRC5.
2010-10-20 | GSE22792 | GEO
Project description:C-mannosylation is a modification of tryptophan residues with a single mannose effecting protein folding, secretion and/or function. To date, only few proteins have been proven to be C-mannosylated and studies aiming at global assessment of protein C-mannosylation from cells or tissues are scarce. In order to interrogate the C-mannosylome of human induced pluripotent stem cells (hiPSCs), we made use of the common finding that C-mannosylation is important for protein secretion. Thus we compared the secretomes of C-mannosyltransferase-deficient DPY19L1 and DPY19L3 mutants to their parental wild-type hiPSCs by mass-spectrometry-based quantitative proteomics. Secretion of numerous proteins was reduced in the mutants.
2021-06-17 | PXD024193 | Pride
Project description:HiPSCs and human myoblast cells were differentiated into myocytes, and the global gene expression profile were analyzed. Comparison of gene expressions among 8 experiments, 3 were derived from hiPSCs(cell line; 253G1), 1 was derived from hiPSCs(cell line; 253G4), 1 was derived from hiPSCs(cell line; 201B7), 2 were from human myoblast cell line (Hu5/E18) and 1 was undifferentiated hiPSCs.
2013-04-01 | E-GEOD-43183 | biostudies-arrayexpress
Project description:Liver fibrosis is characterized by the excessive formation and accumulation of matrix proteins as a result of wound healing in the liver. A main event during fibrogenesis is the activation of the liver resident quiescent hepatic stellate cell (qHSC). Recent studies suggest that reversion of the activated HSC (aHSC) phenotype into a quiescent-like phenotype could be a major cellular mechanism underlying fibrosis regression in the liver, thereby offering new therapeutic perspectives for the treatment of liver fibrosis. The goal of the present study is to identify experimental conditions that can revert the activated status of human HSCs and to map the molecular events associated with this phenotype reversion by gene expression profiling Transcriptomic profiling of primary human quiescent HSCs (qHSCs), in vitro activated HSCs (aHSCs) and in vitro reverted HSCs (rHSCs). The cell types come from different donors (This is detailed in the original manuscript.).
2015-08-12 | E-GEOD-68001 | biostudies-arrayexpress