Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Heterogeneous metabolic signatures are linked to cancer cell differentiation in colorectal cancer

ABSTRACT: Colorectal cancer (CRC) is characterized by functional intratumor heterogeneity that shares many similarites with the hierarchical organization of the normal intestinal epithelium. In order to relate transcriptional subtypes to functional tumor cell heterogeneity we applied scRNA-seq to 12 patient-derived CRC spheroid cultures. We identified shared expression programs that relate to intestinal lineages and revealed metabolic signatures that are linked to cancer cell differentiation. In addition, we validated and complemented sequencing results by quantitative microscopy using live-dyes and multiplexed RNA fluorescence in situ hybridization, thereby revealing metabolic compartmentalization and potential cell-cell interactions. FInally, we demonstrate functional differences between metabolically distinct lineage subtypes that might have strong implications for future treatment strategies of CRC.

PROVIDER: EGAS00001004064 | EGA |

REPOSITORIES: EGA

ACCESS DATA

Json Xml

Similar Datasets

ena-DATASET-DKFZ-27-11-2019-10:10:01:100-632 - samples

Project description:Colorectal cancer (CRC) is characterized by functional intratumor heterogeneity that shares many similarites with the hierarchical organization of the normal intestinal epithelium. In order to relate transcriptional subtypes to functional tumor cell heterogeneity we applied scRNA-seq to 12 patient-derived CRC spheroid cultures. We identified shared expression programs that relate to intestinal lineages and revealed metabolic signatures that are linked to cancer cell differentiation. In addition, we validated and complemented sequencing results by quantitative microscopy using live-dyes and multiplexed RNA fluorescence in situ hybridization, thereby revealing metabolic compartmentalization and potential cell-cell interactions. Finally, we demonstrate functional differences between metabolically distinct lineage subtypes that might have strong implications for future treatment strategies of CRC.

| EGAD00001005524 | EGA

Functional states in tumor-initiating cell differentiation in human colorectal cancer

Project description:Intra-tumor heterogeneity of tumor-initiating cell (TIC) activity drives colorectal cancer (CRC) progression and therapy resistance. Here, we used single-cell mRNA-sequencing (scRNA-seq) of patient-derived CRC models to decipher distinct cell subpopulations based on their transcriptional profiles. Cell type-specific expression modules of stem-like, transit amplifying-like, and differentiated CRC cells resemble differentiation states of normal intestinal epithelial cells. Strikingly, identified subpopulations differ in proliferative activity and metabolic state. In summary, we here show at single-cell resolution that transcriptional heterogeneity identifies functional states during TIC differentiation. Targeting transcriptional states associated to cancer cell differentiation might unravel vulnerabilities in human CRC.

2021-05-07 | PXD018230 | Pride

Consensus Molecular Subtypes of colorectal cancer are recapitulated in in vitro and in vivo models [primary cell lines AMC/Palermo]

Project description:Colorectal cancer (CRC) is a highly heterogeneous disease both from a molecular and clinical perspective. Several distinct molecular entities, such as microsatellite instability (MSI), have been defined that make up biologically distinct subgroups with their own clinical course. Recent data indicated that CRC can be best segregated into four groups called Consensus Molecular Subtypes (CMS1-4), which each have a unique biology and gene expression pattern. In order to develop improved, subtype-specific therapies and to gain insight into the molecular wiring and origin of these subtypes, reliable models are needed. This study was designed to determine the heterogeneity and identify the presence of CMSs in a large panel of CRC cell lines, primary cultures and patient-derived xenografts (PDX). We provide a repository encompassing this heterogeneity and moreover describe that a large part of the models can be robustly assigned to one of the four CMSs, independent of the stromal contribution. We subsequently validate our CMS stratification by functional analysis which for instance shows mesenchymal enrichment in CMS4 and metabolic dysregulation in CMS3. Finally, we observe a clear difference in sensitivity to chemotherapy-induced apoptosis, specifically between CMS2 and CMS4. This relates to the in vivo efficacy of chemotherapy, which delays outgrowth of CMS2, but not CMS4 xenografts. This indicates that molecular subtypes are faithfully modelled in the CRC cell cultures and PDXs, representing tumour cell intrinsic and stable features. This repository provides researchers with a platform to study CRC using the existing heterogeneity.

2017-12-01 | GSE100549 | GEO

Consensus Molecular Subtypes of colorectal cancer are recapitulated in in vitro and in vivo models [patient tumors and PDX models]

2017-12-01 | GSE100480 | GEO

Consensus Molecular Subtypes of colorectal cancer are recapitulated in in vitro and in vivo models [primary cell lines Hubrecht Institute]

2017-12-01 | GSE100479 | GEO

Consensus Molecular Subtypes of colorectal cancer are recapitulated in in vitro and in vivo models [cell line panel]

2017-12-01 | GSE100478 | GEO

Deep transcriptional profiling of the two cancer stem cell populations present in the SW480 cell line as presented in "Colorectal Cancer Stem Cell Subtypes Orchestrate Distinct Tumor Microenvironments" [bulk RNA-seq]

Project description:Tumor heterogeneity derives from diverse populations of cancer cells that contribute unique properties to the microenvironment and tumor progression. While multiple classification systems have been developed to define tumor subtypes in colorectal cancer (CRC), the lack of single cell resolution has prohibited a better understanding of how these distinct cancer cell subtypes influence the overall tumor phenotype. Here were report that two cancer stem cell subtypes that are oncogenic versions of the intestinal Crypt Base Columnar (CBC) and Regenerative Stem Cell (RSC) populations, are commonly co-present in human CRC. We develop subtype-specific xenograft models utilizing a heterogeneous patient cell line (SW480) that contains CBCs and RSCs, and we define their tumor microenvironments at high resolution via single cell RNA sequencing. RSCs create differentiated, inflammatory, slow growing tumors. CBCs create proliferative, immune-suppressive, invasive tumors. With this enhanced resolution, we unify current CRC patient classification schema with TME phenotypes and organization.

2024-04-25 | GSE254891 | GEO

Single cell profiling of SW480 subtype-specific subcutaneous and orthotopic xenografts (SW480-CBC and SW480-RSC) as presented in "Colorectal Cancer Stem Cell Subtypes Orchestrate Distinct Tumor Microenvironments" [scRNA-seq]

2024-04-25 | GSE254890 | GEO

Luciferase Expressing Preclinical Model Systems Representing the Different Molecular Subtypes of Colorectal Cancer

Project description:We established combined 2D/3D, in vitro/in vivo model systems representing the heterogeneity of colorectal cancer (CRC) with regards to different molecular subtypes. Comparative characterization of stable luciferase expressing derivatives of well-established CRC cell lines, derived spheroids and subcutaneous xenograft tumors showed that the 3D-spheroid cultures resembled xenografts more closely than 2D-cultured cells do. The model systems can be used in preclinical research applications to study new therapy approaches and represents the biological heterogeneity of CRC.

2023-10-10 | GSE241569 | GEO

Molecular signatures of heterogeneous stem cell populations are resolved by linking single cell functional assays to single cell gene expression

Project description:The discovery of significant heterogeneity in the self-renewal durability of adult haematopoietic stem cells (HSCs) has challenged our understanding of the molecules involved in population maintenance throughout life. Gene expression studies in bulk populations are difficult to interpret since multiple HSC subtypes are present and HSC purity is typically less than 50% of the input cell population. Numerous groups have therefore turned to studying gene expression profiles of single HSCs, but again these studies are limited by the purity of the input fraction and an inability to directly ascribe a molecular program to a durable self-renewing HSC. Here we combine single cell functional assays with flow cytometric index sorting and single cell gene expression assays to gain the first insight into the gene expression program of HSCs that possess durable self-renewal. This approach can be used in other stem cell systems and sets the stage for linking key molecules with defined cellular functions. single-cell RNA-Seq of haematopoietic stem cells

2015-05-26 | E-GEOD-61533 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data