Whole transcriptome analysis of iPSC derived hepatic organoids cultures
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PROVIDER: PRJNA576358 | ENA |
REPOSITORIES: ENA
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Project description:A heatmap, which focused upon 2458 genes that were involved in stem cell differentiation and liver development, was prepared to visualize the relative relationship between the transcriptomes of iPSCs, PHHs, human liver tissue and HO1. The dendrogram indicates that HO1 is more closely related to liver tissue than to PHHs; this is because cholangiocytes are present in HO1 and liver, but are absent (or rare) in PHHs. Examination of the genes within this heatmap indicated that there was a lack of expression of pluripotent genes in HO1; and that HO1 had an increased level of expression of cellular markers for liver lineages and liver development, which included mature hepatocytes, bile duct cells and NOTCH signaling components. A cluster analysis of 1510 genes indicates that there were major changes in the transcriptome after the cells that were dissociated from an HO1 were transferred from the growth medium into the differentiation medium. As with the HO1s, the gene expression profile of HO2s resembled that of PHHs and human liver. Of importance, the level of expression of mRNAs that are of importance for various human liver functions (ADH4, CYP3A4, TTR, GSRA1, TDO2, GSTA1 and FAH) were markedly increased in HO2s.
2017-10-21 | GSE101770 | GEO
Project description:A heatmap, which focused upon 2458 genes that were involved in stem cell differentiation and liver development, was prepared to visualize the relative relationship between the transcriptomes of iPSCs, PHHs, human liver tissue and HO1. The dendrogram indicates that HO1 is more closely related to liver tissue than to PHHs; this is because cholangiocytes are present in HO1 and liver, but are absent (or rare) in PHHs. Examination of the genes within this heatmap indicated that there was a lack of expression of pluripotent genes in HO1; and that HO1 had an increased level of expression of cellular markers for liver lineages and liver development, which included mature hepatocytes, bile duct cells and NOTCH signaling components. A cluster analysis of 1510 genes indicates that there were major changes in the transcriptome after the cells that were dissociated from an HO1 were transferred from the growth medium into the differentiation medium. As with the HO1s, the gene expression profile of HO2s resembled that of PHHs and human liver. Of importance, the level of expression of mRNAs that are of importance for various human liver functions (ADH4, CYP3A4, TTR, GSRA1, TDO2, GSTA1 and FAH) were markedly increased in HO2s.
2019-10-09 | GSE138549 | GEO
Project description:Thyroid hormone (TH) levels are low during development, and the deiodinases control TH signaling through tissue-specific activation or inactivation of TH. Here we studied human iPSC-derived hepatic organoids and identified a robust induction in DIO2 expression (the deiodinase that activates T4 to T3) that occurs in hepatoblasts. The surge in D2-T3 persists until the hepatoblasts differentiate into hepatocytes- or cholangiocytes-like cells, neither of which express DIO2. Preventing the induction of the D2-T3 signaling modified the expression of key transcription factors, decreased the number of hepatocyte-like cells by ~60%, and increased the number of cholangiocyte-like cells by ~55% without affecting the growth or the size of the mature liver organoid. Physiological levels of T3 could not fully restore the transition from hepatoblasts to mature cells. This indicates that the timed surge in D2-T3 signaling critically determines the fate of developing human hepatoblasts and the transcriptome of the maturing hepatocytes, with physiological and clinical implications for how the liver handles energy substrates.
2024-01-24 | GSE245250 | GEO
Project description:Experiment intended to obtain expression profiles of iPSC-derived human colon organoids compared to undifferentiated human iPSCs and a patient-derived colon organoid line
2021-10-25 | E-MTAB-11026 | biostudies-arrayexpress
Project description:We analyzed gene expression profiles of self-organizing, multi-cellular, 3D liver organoids derived by co-culture of induced Pluripotent Stem Cell and stromal progenitors. We report the RNA-seq results of liver organoid at day0, day2, day4, day6 of co-culture. We also report RNA-seq results of constituent of the liver organoid, which are human iPSC at hepatic specification stage, human Mesenchymal stem cells derived from bone marrow, human umbilical vein endothelial cell. As controls, we also report RNS-seq results of un-differentiated human iPSC, human iPSC at definitive endoderm stage, human liver tissue, and primary cultured human hepatocytes isolated from unused donor livers.
2017-03-14 | GSE85223 | GEO
Project description:Retinitis pigmentosa (RP) is an irreversible and inherited retinopathy. RPGR mutations are the most common causes of this disease. It remains challenging to decipher the mechanism of RPGR mutation because of the lack of appropriate study models. The substitution of patient-specific diseased retina without ethical restrictions is desired and iPSC-derived 3D retina is the best choice. In our experiment, we generated iPSCs from one RP patient with 2-bp frameshift mutation in the exon14 of RPGR gene, which were differentiated into retinal organoids. Also we generated iPSCs from a normal control and differentiated those control-iPSCs into healthy retinal organoids. Samples of patient- and control-retinal organoids at W0, W7, W13 (two replicates), W18 (two replicates) and W22 (two replicates for patient) were collected for RNA-seq. Corrected-iPSC were derived from CRISPR/Cas9-mediated gene correction. Then we collected the corrected-iPSC derived retinal organoids at W0, W7, W13 (two replicates), W18 (two replicates) and W22 (two replicates) for RNA-seq. Through the RNA-seq data, we demonstrate that patient-specific iPSC-dervied 3D retinae can recapitulate disease progress of Retinitis Pigmentosa through presenting defects in photoreceptors' gene profile. CRISPR/Cas9-mediated gene correction can rescue photoreceptor gene profile. Those transcriptome are consistent with the phenotype and function.
2020-02-01 | E-MTAB-6490 | biostudies-arrayexpress
Project description:Hepatic organoids are a recent innovation in in vitro modelling. Initial studies suggest organoids better recapitulate the liver phenotype in vitro compared to pre-existing proliferative cell models. However, their propensity for drug metabolism and detoxification remains poorly characterised. A global proteomic profiling of undifferentiated and differentiated hepatic murine organoids and donor-matched livers was therefore performed to assess both their similarity to liver tissue and DMET expression. iTRAQ analysis revealed 4,405 proteins commonly detected across all sample types. Differentiation of organoids significantly increased the expression of multiple CYP450s, phase II enzymes, liver biomarkers and hepatic transporters. While the final phenotype of differentiated organoids is distinct from liver tissue, they contain multiple DMET proteins necessary for liver function and drug metabolism, such as CYP450 3A, GSTA and MDR1A. Hepatic organoids may therefore represent an attractive novel model for hepatotoxicity testing, although further experimentation, optimisation and characterisation is needed relative to pre-existing models to fully contextualise their use as a putative in vitro model of DILI.
2021-06-03 | PXD017986 | Pride
Project description:Purpose: A proof of concept study examining the disease modelling capabilities of patient iPSC derived kidney organoids. Methods: A proband was diagnosed by genome sequencing with compound heterozygous IFT140 mutations. A one-step reprogramming/gene-editing protocol of proband fibroblasts was used to derive both uncorrected patient and isogenic gene-corrected induced pluripotent stem cells (iPSC) which were differentiated to kidney organoids. Organoids were examined by immunofluorescence. Additionally, epithelial cells magnetically sorted from whole kidney organoids underwent transcriptional profiling and spheroid culture. Results: Differential expression analysis of organoid epithelial cell fractions demonstrated apicobasal polarity, cell-cell junction and dynein motor assembly downregulation in patient organoids. Defective ciliary morphology and spheroid culture were rescued in gene corrected organoids. Conclusions: This study validates patient iPSC-derived kidney organoids as a novel, faithful and patient-specific model to further the study of inherited renal disease in regenerated, human, in vitro tissue.
2018-04-26 | GSE107230 | GEO
Project description:Gene expression profile of human iPSC-derived lacrimal gland-like organoids.
2022-01-10 | GSE174653 | GEO
Project description:Microglia are specialised brain-resident macrophages that arise from primitive macrophages colonising the embryonic brain. Microglia contribute to multiple aspects of brain development, but their precise roles in early human brain remain poorly understood due to limited access to relevant tissues. The generation of brain organoids from induced human pluripotent stem cells (iPSC) recapitulates some key features of human embryonic brain development, but current approaches do not incorporate microglia and thus are lacking. Here, we generated microgliasufficient brain organoids by co-culturing brain organoids with primitive-like macrophages generated from the same human iPSC (iMac). In organoid co-cultures, iMac differentiated into cells with microglia-like phenotypes and functions (iMicro), and modulated neuronal progenitor cell (NPC) differentiation, limiting NPC proliferation and promoting axonogenesis. Mechanistically, iMicro contained high levels of PLIN2+ lipid droplets that exported cholesterol and its esters which weretaken up by NPC in the organoids. We also detected PLIN2+ lipid droplet-loaded microglia in mouse and human embryonic brain. Overall, our approach significantly advances current human brain organoid approaches by incorporating microglial
2023-09-16 | GSE242894 | GEO