577705e9-e32d-4db2-aaf8-1b9e1d9aee04 - samples
Ontology highlight
ABSTRACT:
PROVIDER: EGAD00001008830 | EGA |
REPOSITORIES: EGA
Similar Datasets
Project description:RNASeq data generated from organoid cultures established from normal gastrointestinal organoids, long-term and paired tumor frozen tissues.
| EGAD00001015421 | EGA
Project description:Intestinal organoids have widespread applications across a variety of fields, but the dependency on basement membrane extract (BME) has hampered the transition towards clinical utilization. To overcome the limitations of BMEs, we identified an easy-to-use and fully defined extracellular matrix for the culture of human colon organoids established directly from tissue biopsies. Human colonic organoids were established from crypt-derived single cells (from six different patient samples) and cultured in QGel® CN99 or the BME benchmark Matrigel® for six culture passages (median 58 days), after which RNA was harvested for further analysis. The CN99 matrix effectively enabled organoid formation and growth, as well as efficient cell expansion, completely by-passing the use of BME. We expect this fully defined matrix to improve the reproducibility of organoid studies and to advance the translational use of the organoid technology.
2020-09-12 | GSE147133 | GEO
Project description:As metabolic rewiring is crucial for cancer cell proliferation, metabolic phenotyping of patient-derived organoids is desirable to identify drug-induced changes and trace metabolic vulnerabilities of tumor subtypes. We established a novel protocol for metabolomic and lipidomic profiling of colorectal cancer organoids by LC-QTOF-MS facing the challenge of capturing metabolic information from minimal sample amount (< 500 cells/injection) in the presence of extracellular matrix (ECM). The best procedure of the tested protocols included ultrasonic metabolite extraction with acetonitrile/methanol/water (2:2:1, v/v/v) without ECM removal. To eliminate ECM-derived background signals, we implemented a data filtering procedure based on p-value and fold change cut-offs which retained features with signal intensities >120% compared to matrix-derived signals present in blank samples. As a proof-of-concept, the method was applied to examine the early metabolic response of colorectal cancer organoids to 5-fluorouracil treatment. Statistical analysis revealed dose-dependent changes in the metabolic profiles of treated organoids including elevated levels of 2'-deoxyuridine, 2'-O-methylcytidin, inosine and 1-methyladenosine and depletion of 2'-deoxyadenosine and specific phospholipids. In accordance with the mechanism of action of 5-fluorouracil, changed metabolites are mainly involved in purine and pyrimidine metabolism. The novel protocol provides a first basis for the assessment of metabolic drug response phenotypes in 3D organoid models.
2021-10-12 | MTBLS2130 | MetaboLights
Project description:Here we have provided scRNAseq datasets of unguided human brain organoids. The organoids were sequenced as a 1) Timecourse, 2) With different extracellular matrix treatments, 3) chemical treatment and 4) from organoids ere generated with a gene knockout cell line. Brain organoids enable the mechanistic study of human brain development, and provide opportunities to explore self-organization in unconstrained developmental systems. We have established long-term, live light sheet microscopy on unguided brain organoids generated from fluorescently labeled human induced pluripotent stem cells, which enables tracking of tissue morphology, cell behaviors, and subcellular features over weeks of organoid development. Based on imaging and single-cell transcriptome modalities, we find that lumenal expansion and cell morphotype composition within the developing neuroepithelium are associated with modulation of gene expression programs involving extracellular matrix (ECM) pathway regulators and mechanosensing. We show that an extrinsically provided matrix enhances lumen expansion as well as telencephalon formation, and unguided organoids grown in the absence of an extrinsic matrix have altered morphologies with increased neural crest and caudalized tissue identity. Matrix induced regional guidance and lumen morphogenesis are linked to the WNT and Hippo (YAP1) signaling pathways, including spatially restricted induction of the Wnt Ligand Secretion Mediator (WLS) that marks the earliest emergence of non-telencephalic brain regions. Altogether, our work provides a new inroad into studying human brain morphodynamics, and supports a view that matrix-linked mechanosensing dynamics play a central role during brain regionalization.
2025-04-30 | E-MTAB-15057 | biostudies-arrayexpress
Project description:Tubuloids offer a powerful tool for advancing renal research and improving patient care. To facilitate this, we have established a robust biobank of 40 adult human kidney organoids derived from fresh or frozen biopsies. These organoids exhibit diverse morphologies, distal and proximal tubules, closely resembling their tissue of origin. We have extensively characterized these organoids using a combination of techniques, including histological staining, immunofluorescence, gene expression analysis (qPCR and RNA-seq), and genetic profiling (STRs). This comprehensive characterization ensures the quality and reliability of the organoids for downstream applications. Molecular analysis revealed the expression of genes characteristic of various kidney cell types. Furthermore, we have successfully cultured these organoids within microfluidic chips, demonstrating their compatibility with advanced culture systems. This platform of well-characterized, living human kidney organoids from fresh and frozen tissues provides a valuable resource for a wide range of biomedical research, including drug screening, disease modeling, and personalized medicine.
2026-07-01 | GSE336733 | GEO
Project description:Non-gestational choriocarcinoma (NGC) is a rare subtype of malignant germ cell tumor. We established a patient-derived xenograft (PDX) model using tumor tissue from an 18-year-old patient with NGC. Then, we performed mRNA-seq analysis using the fresh-frozen tissues of the original tumor and the PDX model.
2023-05-03 | GSE230352 | GEO
Project description:Recently, oncology has moved to a new clinical practice, more personalized, called Predictive Oncology (PO).
PO comes from our knowledge about tumor heterogeneity that implies that each disease, thus each patient, is unique. PO’s goal is to identify and administrate the right treatment to the right patient.
For this, PO requires to go through 3 majors steps:
1. A good characterization of the tumor to identify candidates,
2. A well-established panel of drugs targeting the identified candidates,
3. A relevant model to functionally test these candidates.
The first point could easily be addressed with recent technologies that now allow the Next Generation Sequencing (NGS) and/or the simultaneous analysis of transcriptomic profiles from thousands of patients. The last two points have not been efficiently achieved so far, which prevents PO to be really efficient.
Indeed, even if NGS allows the identification of potential targets, the presence of a molecular candidate does not necessary means obligatory functional response.
The number of drugs approved by the Food and Drug Administration remains limited and most frequent targets in solid tumors (for ex. RAS, P53, MYC, RB1 ...) still do not have specific drugs approved in clinic.
Finally, available pre-clinical models still present many major inconvenient:
* Chimiogrammes on 2D cultures are not sufficiently relevant to be really predictive of the in vivo situation;
* Patient derived xenograft (PDX) are not adapted for clinical use because not all tumors graft and the time to develop a PDX is too long (several months), thus incompatible with the history of the disease (especially for most severe patients). Furthermore the host (NOD-SCID mouse) is immuno-depressed, preventing to objectively test antibodies-mediated drugs.
Recently, the 3D cell culture technology has proven its superiority to predict drug response over classical 2D chimiogrammes. It consists in growing "mini-tissues", or organoid-derived from tumor/healthy tissues, thanks to the amplification of stem cells contained within the sample. The generated organoids are personalized and biologically relevant (organoids are expend form the patient’s stem cells which self-organized according to the architecture of the tissue they are originating from), they are genetically stable, their growth is compatible with patient’s disease history (organoids grow in few weeks), easy and convenient to achieve, even from small biological material quantities (0.5< x < 1cm3), and they can be amplified, frozen and thawed on demand. Moreover, organoids can be made more complex with the addition of other cell types (fibroblasts, immune cells ...). None of the actual available pre-clinical model regroups all these characteristics.
The constitution of a "next generation" biobank of liver samples (Metastases to the liver and Hepato Cellular Adenocarcinoma) will be very useful in the context of predictive oncology.
For this, a biopsy needs to be dissociated and grown in Matrigel, in presence of a well-defined list of growth factors. Once the culture is established, organoids can be frozen then defrost on demand.
Our main objective is to evaluate the feasibility for building a biobank of liver-derived organoids, from liver metastases of colorectal cancers, hepatocellular adenoma and adenocarcinoma (waste tissues).
Applications related to organoids derived from tumors are quasi indefinite, from drug screening assays, tests for novel therapies or original drug combinations, to patients’ stratifications or fundamental research.
In our case, we are interested in building this a biobank in the prospect of using it to build the "next generation of model for predictive oncology" to study liver-related cancers and related drugs testing. Briefly, we want to implement these organoids with cells from the microenvironment in order to makes the global model more pertinent for drug testing.
If successful, the generation of such biobank, including both tumor-derived organoids and healthy counterpart, could be really helpful for the scientific and medical community.
| 2731334 | ecrin-mdr-crc
Project description:RNASeq data generated from organoid cultures established from gastric cancers and normal mucosae, paired tumor frozen tissues, and cultured fibroblast.
| EGAD00001004302 | EGA
Project description:This model builds upon two published models focused on the early steps of metastasis by Cohen et al. and on EMT process by Selvaggio et. al. The initial model of Cohen and colleagues was built with two inputs: the ECMenv, which monitored the status of the extracellular matrix, and DNA_damage, which considered DNA alterations that trigger death signals. Four additional inputs were added to account for the presence of Oxygen, growth factors (as GF), TGFbeta and the contact with other neighboring cells (as Neigh). The phenotypes, or outputs of the model include CellCycleArrest, Apoptosis, EMT, ECM_adh (for cell adhesion), ECM_degrad (for cell degradation), Cell_growth (for the dynamics of the tumor growth) and Cell_freeze (for cell motility ability). New genes and pathways include mechanisms around p63 and SRC. Genes from the Hippo pathway and RhoGTPases, such as YAP1, FAK and RAC1 were also inserted to link external signals (i.e., cell–cell contact, stiffness of the extracellular matrix, and stress signals) and intracellular regulation. The resulting network encompasses 45 nodes, with 6 input nodes, representing the possible interactions of an individual cell with external elements, and 8 output nodes or read-outs describing the possible observed phenotypes.
This model was initially developed as a MaBoSS model for a multi-scale model of tumor invasion, developed with PhysiBoSS. As SBML-qual cannot describe fully a MaBoSS model yet, we also include the MaBoSS BND and CFG files.
2023-06-27 | MODEL2304070002 | BioModels
Project description:Background and aims: Cell-cell adhesion structures (desmosomes and, especially, tight junctions) are known to play important roles in control of transepithelial permeability in the colon. The involvement of cell-matrix interactions in permeability control is less clear. The goals of the present study were to: i) determine if disruption of colon epithelial cell interactions with the extracellular matrix alters permeability control and ii) determine if increasing the elaboration of protein components of cell-matrix adhesion complexes improves permeability control and mitigates the effects of cell-matrix disruption. Results: Treatment of colon organoids with Aquamin® increased the expression of multiple basement membrane and hemidesmosomal proteins as well as keratin 8 and 18. TEER values were higher in the presence of Aquamin® than they were under control conditions. Conclusions: These findings provide evidence that cell-matrix interactions contribute to permeability control in the colon. They suggest that the elaboration of proteins important to cell-matrix interactions can be increased in human colon organoids by exposure to a multi-mineral natural product. Increasing the elaboration of such proteins may help to mitigate the consequences of disrupting cell-matrix interactions on permeability control.
2022-03-14 | PXD026923 | Pride