RNAseq of patient-derived colon organoids treated with 3PO for 24h
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE270210 | GEO | 2024/06/26
REPOSITORIES: GEO
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Project description:RNAseq of patient-derived colon organoids treated with 3PO for 24h
| PRJNA1125411 | ENA
Project description:Huntsman Cancer Institute (HCI)-001 patient-derived organoids (PDOs) and HCI-002 PDOs obtained from Huntsman Cancer Institute, University of Utah (Nat Med. 2011 Oct 23;17(11):1514-20). Purpose: The goals of this study is to identify molecular pathways and genes that are involved in the treatment responsiveness of breast cancer PDOs. Methods: mRNA profiles of HCI-001 and HCI-002 PDOs were generated by Illumina NovaSeq 6000 platform for paired-end sequencing, 150-bp read length, for about 20 million raw reads per sample. RNA sequencing FASTQ files were processed with HISAT2 aligner in default mode with the Ensembl human transcriptome annotation (Build version GRCh38 and transcript annotation GRCh38.89). Differential gene expression analysis was performed using DESeq2 software. Enrichment analysis was performed using ClusterProfiler software. Results: We mapped about 20 million sequence reads per sample to the human genome (build HG38) in the RNAs of HCI-001 and HCI-002 PDOs treated with paclitaxel or vehicle. We used a minimum expression cut-off of 1 FPKM in order to exclude low-levels genes and the RNA-seq data confirmed the difference expression of 67 known apoptosis-regulatory genes in treatment-sensitive PDOs (HCI-002) compare to treatment-resistant PDOs (HCI-001). Conclusions: This study identified apoptosis-regulatory genes that are differentially induced or represeed in treatment-sensitive PDOs (HCI-002) or treatment-resistant PDOs (HCI-001).
2021-09-09 | GSE183477 | GEO
Project description:Brain tumors are the leading cause of cancer-related death in children. Experimental in vitro models that faithfully capture the hallmarks and tumor heterogeneity of pediatric brain cancer are limited and hard to establish. We present a protocol that enables efficient generation, expansion and biobanking of pediatric brain cancer organoids. Utilizing our protocol, we have established patient-derived organoids (PDOs) from ependymomas, medulloblastomas, low-grade glial tumors and patient-derived xenograft organoids (PDXOs) from medulloblastoma xenografts. PDOs and PDXOs recapitulate histological features, DNA methylation profiles and intratumor heterogeneity of the tumors from which they were derived. We also showed that PDOs can be xenografted. Most interestingly, when subjected to the same routinely applied therapeutic regimens, PDOs respond similarly to the patients. Taken together, our study highlights the potential of PDOs and PDXOs for research and translational applications for personalized medicine.
2023-12-01 | GSE247231 | GEO
Project description:Brain tumors are the leading cause of cancer-related death in children. Experimental in vitro models that faithfully capture the hallmarks and tumor heterogeneity of pediatric brain cancer are limited and hard to establish. We present a protocol that enables efficient generation, expansion and biobanking of pediatric brain cancer organoids. Utilizing our protocol, we have established patient-derived organoids (PDOs) from ependymomas, medulloblastomas, low-grade glial tumors and patient-derived xenograft organoids (PDXOs) from medulloblastoma xenografts. PDOs and PDXOs recapitulate histological features, DNA methylation profiles and intratumor heterogeneity of the tumors from which they were derived. We also showed that PDOs can be xenografted. Most interestingly, when subjected to the same routinely applied therapeutic regimens, PDOs respond similarly to the patients. Taken together, our study highlights the potential of PDOs and PDXOs for research and translational applications for personalized medicine.
2023-12-01 | GSE247380 | GEO
Project description:Recent data suggests that colon tumors contain a subpopulation of therapy resistant quiescent cancer stem cells (qCSCs) are the source of relapse following treatment. The isolation and molecular characterisation of qCSCs may therefore lead to the identification of novel therapeutic targets for their elimination. Label retention of the lipophilic fluorescent dye PKH26, wherein dividing cells lose the label and quiescent or slow cycling cells retain the label for an extended period of time, was used to isolate qCSCs from a panel of colon cancer patient-derived organoids (PDOs). PDOs were dissociated to single cells, labelled with PKH26 and plated in Matrigel culture. After 12 days, PDOs were processed to single cells, labelled with DAPI (to exclude dead cells) and isolated by fluorescence assisted cell sorting (FACS) into two fractions of PKH26-Negative and PKH26-Positive (label retaining) cells. Functional analyses of these cellular subpopulations demonstrated that PKH26-Positive cells are self-renewing qCSCs. RNA was collected from FAC sorted PKH26-Negative and PKH26-Positive cells and analysed by RNA-sequencing. Cells were lysed in RLTplus buffer and RNA was extracted using Qiagen RNeasy Mini Kit. RNA quality was assessed prior to sequencing. Samples were processed using NuGEN’s Ovation RNA-Seq System V2 and Ultralow V2 Library System and sequenced on an Illumina HiSeq 2500 machine as 2x125nt paired-end reads. Reads were mapped to the human reference genome (assembly hg19) using the STAR aligner (version 2.4.2a). Total read counts per gene were computed using the program “featureCounts” (version 1.4.6-p2) in the “subread” package, with the gene annotation taken from Gencode (version 19).
2021-02-08 | E-MTAB-8924 | biostudies-arrayexpress
Project description:In our study, we aimed to investigate adaptive processes of tumors under treatment and therefore, generated PDAC patient-derived organoids (PDOs) and 2D cell lines before and after chemotherapy. We enrolled a patient with borderline resectable PDAC who received neoadjuvant FOLFIRINOX. Endoscopic fine needle (pre-FFX) and surgical biopsies (post-FFX) were used to generate PDOs and 2D cells. Whole exome sequencing (WES) and RNA sequencing data of the pre-FFX and post-FFX organoids were compared in order to evaluate the genetic landscape and PDAC subtypes. Although transcriptional subtyping classified both PDOs as classical PDAC, gene set enrichment analysis (GSEA) revealed a reduced pathway activation linked to the basal-like phenotype such as KRAS signaling in the post-FFX organoids. WES did not show major differences in the genetic landscape of the tumor pre- and post-FFX induction suggesting a plasticity process rather than a clonal selection during chemotherapy. 2D cells were subjected to an unbiased automated drug screening of 415 compounds to investigate FFX-induced vulnerabilities. Top targets such as MEK inhibitors were validated manually in the 2D cells and organoids and an increased sensitivity was observed in the post-FFX cells. Thus, integrating functional layers into personalized medicine allows to identify chemotherapy-induced vulnerabilities as potent targeted therapy options in PDAC.
2022-03-09 | GSE193389 | GEO
Project description:Patient derived organoids (PDOs) closely resemble individual tumor biology. They are thus promising models for drug discovery and precision medicine. Here, we describe high-throughput imaging and automated image analysis of PDOs. We generated PDOs from colorectal cancer patients. Subsequently, we treated them with >500 substances to capture almost 6 million images by confocal microscopy. We developed a software framework to analyze how perturbations alter the organization of multicellular PDOs. Therewith, we observed a rich spectrum of reoccurring phenotypes. Targeting cellular processes, including signaling by MEK, GSK3 or CDKs, led to distinct architectural changes. Also, we detected compound-induced phenotypes only present in subsets of PDOs with specific molecular alterations. Finally, PDO response to anticancer drugs matched the clinical course of corresponding patients. The presented high-throughput imaging workflow and data allow compound profiling with complex multicellular organoid models for drug discovery and personalized medicine. We used microarrays to detail the global programme of gene expression underlying different lines of patient-derived colorectal cancer organoids.
2019-03-03 | GSE117548 | GEO
Project description:Here we present the generation and characterization of patient-derived organoids (PDOs) from colorectal cancer patients. Two PDOs derived from patients with TP53 mutations were tested with two different HDACIs (SAHA and NKL54). Induction of cell death, transcriptome, and chromatin accessibility changes were analyzed. HDACIs promote the upregulation of low expressed genes and suppress the expression of highly expressed genes. A similar differential effect is also observed at the level of chromatin accessibility. Only SAHA is a potent inducer of cell death. The induction of apoptosis is characterized by the upregulation of BH3-only genes (especially BIK and BMF). Up-regulation of BIK is associated with increased accessibility in an intronic region. SAHA, but not NKL54, also causes downregulation of BCL2L1 and decreases chromatin accessibility in three distinct regions of the BCL2L1 locus. Both inhibitors upregulate the expression of innate immunity genes and members of the MHC family. In conclusion, our studies explain the mechanisms of action of SAHA and cast doubt on the use of NKL54 as a single agent for efficient apoptosis induction.
2024-03-04 | GSE246045 | GEO
Project description:Here we present the generation and characterization of patient-derived organoids (PDOs) from colorectal cancer patients. Two PDOs derived from patients with TP53 mutations were tested with two different HDACIs (SAHA and NKL54). Induction of cell death, transcriptome, and chromatin accessibility changes were analyzed. HDACIs promote the upregulation of low expressed genes and suppress the expression of highly expressed genes. A similar differential effect is also observed at the level of chromatin accessibility. Only SAHA is a potent inducer of cell death. The induction of apoptosis is characterized by the upregulation of BH3-only genes (especially BIK and BMF). Up-regulation of BIK is associated with increased accessibility in an intronic region. SAHA, but not NKL54, also causes downregulation of BCL2L1 and decreases chromatin accessibility in three distinct regions of the BCL2L1 locus. Both inhibitors upregulate the expression of innate immunity genes and members of the MHC family. In conclusion, our studies explain the mechanisms of action of SAHA and cast doubt on the use of NKL54 as a single agent for efficient apoptosis induction.
2024-03-04 | GSE246044 | GEO
Project description:In this study, we have generated patient-derived organoids (PDOs) from primary and metastatic lesions of gastrointestinal cancers, including pancreatic ductal adenocarcinoma, colorectal adenocarcinoma, and cholangiocarcinoma and evaluated their ability to predict donor tumor drug response. Specifically, we examined individual PDO responses to therapeutic agents with the observed clinical responses of donor patients to the same treatments and demonstrated an approximately 80% concordance rate. Importantly, we found a profound influence of culture media in PDOs phenotypes, we observed a significant difference in response to common PDAC chemotherapies, distinct morphologies, and transcriptomes between media in the same PDOs. These studies demonstrate the important role of culture media when using PDOs to inform patient care and predict response across a spectrum of GI cancers. We compared transcriptome data from pancreatic ductal adenocarcinoma patient-derived organoids in two media (WNT and PaTOM).
2022-10-12 | GSE212014 | GEO