Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Stem cell-associated heterogeneity in Glioblastoma results from intrinsic tumor plasticity shaped by the microenvironment

ABSTRACT: Cancer stem cells (CSCs) have been proposed to underlie the hierarchical organization of Glioblastoma (GBM) causing resistance to treatment, however the identity of CSCs in solid tumors remains largely elusive. Here we find that GBM cells expressing cell membrane CSC-associated markers do not represent a clonal entity defined by distinct functional properties and/or transcriptomic profiles, but rather a plastic state that most cancer cells can adopt. We show that phenotypic heterogeneity arises from non-hierarchical, reversible state transitions that are instructed by the microenvironment. While all tested cancer cell subpopulations survive and adjust their phenotype in vivo, their speed of plasticity differs resulting in variable tumor growth rates. Thus CSC-associated phenotypic heterogeneity is a result of stochastic reversible plasticity and increased tumorigenic potential in vivo correlates with fast adapting cell states.

ORGANISM(S): Homo sapiens

PROVIDER: GSE128195 | GEO | 2019/03/26

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Expression data from CSC and Non-CSC of three HCC cell lines

Project description:Hepatocellular carcinoma (HCC) represents the major subtype of liver cancer, characterized with a high rate of recurrence and heterogeneity. Liver cancer stem cells (CSCs) may account for a hierarchical organization of heterogeneous cancer cells. However, how liver CSCs sustain their self-renewal remains largely unknown. We used microarrays to discover the long non-coding RNAs (lncRNAs) expression underlying cell stem cell (CSC) and non cell stem cell (non-CSC) and identified distinct lncRNAs during this process. We sorted CD13+CD133+ and CD13-CD133- cells from Hep3B, Huh7, and PLC/PRF/5 HCC cell lines as liver CSCs and non-CSCs, then hybridized on Affymetrix microarrays. We sought to identify distinct lncRNAs in liver CSCs.

2015-03-05 | E-GEOD-66529 | biostudies-arrayexpress

Expression data from CSC and Non-CSC of three HCC cell lines

2015-03-05 | GSE66529 | GEO

Expression data from CSC and Non-CSC of three primary HCC samples

2019-07-10 | GSE122420 | GEO

Phenotypic plasticity determines cancer stem cell therapeutic resistance in oral squamous cell carcinoma I

Project description:Cancer stem cells (CSCs) drive tumour spread and therapeutic resistance, and can undergo epithelial-to-mesenchymal transition (EMT) and mesenchymal-to-epithelial transition (MET) to switch between epithelial and post-EMT sub-populations. Examining oral squamous cell carcinoma (OSCC), we now show that increased phenotypic plasticity, the ability to undergo EMT/MET, underlies increased CSC therapeutic resistance within both the epithelial and post-EMT sub-populations. The post-EMT CSCs that possess plasticity exhibit particularly enhanced therapeutic resistance and are defined by a CD44highEpCAMlow/-CD24+ cell surface marker profile. Treatment with TGFÎ² and retinoic acid (RA) enabled enrichment of this sub-population for therapeutic testing, through which the endoplasmic reticulum (ER) stressor and autophagy inhibitor Thapsigargin was shown to selectively target these cells. Demonstration of the link between phenotypic plasticity and therapeutic resistance, and development of an in vitro method for enrichment of a highly resistant CSC sub-population, provides an opportunity for the development of improved chemotherapeutic agents that can eliminate CSCs. The CA1 OSCC cell line was sub-cloned to derive 4 clonal sub-lines, termed pEMT-P, pEMT-S, Epi-S and Epi-P (here 18, 23, 7 and 4 respectively).

2016-01-12 | E-GEOD-74578 | biostudies-arrayexpress

Expression data from cancer stem cells derived from colorectal organoids

Project description:Colorectal cancer (CRC) is characterized by extensive intra-tumor heterogeneity. The cancer stem cell (CSC) theory may explain the mechanisms underlying the non-genetic heterogeneity and their characteristics of prominent plasticity are emerging to be elucidated. By tracking the spheroid formation and growth capacity of CRC CSCs with a single-cell resolution using an organoid culture, we revealed CSCs consisted of subpopulations with a dual (fast and slow)-growing pattern. When isolated, the slow-growing CSCs remained slow-growing and converted into dual-growing CSCs under certain conditions. The slow-growing cells showed low levels of MAP kinase activity and were resistant to a MEK1/2 inhibitor as well as chemo-drugs. The MSI1 gene was down-regulated in the slow-growing CSCs and played a key role in the transition between slow- and dual-growing CSCs. Isolation of slow-growing CSCs will provide a platform to elucidate the role of the plasticity of CSCs in drug resistance and tumor recurrence. To disclose the molecular characteristics of the CSC subclones with the distinct growth features, we analyzed the differentially expressed genes between the subgroups.

2021-10-01 | GSE185012 | GEO

Phenotypic plasticity determines cancer stem cell therapeutic resistance in oral squamous cell carcinoma II

Project description:Cancer stem cells (CSCs) drive tumour spread and therapeutic resistance, and can undergo epithelial-to-mesenchymal transition (EMT) and mesenchymal-to-epithelial transition (MET) to switch between epithelial and post-EMT sub-populations. Examining oral squamous cell carcinoma (OSCC), we now show that increased phenotypic plasticity, the ability to undergo EMT/MET, underlies increased CSC therapeutic resistance within both the epithelial and post-EMT sub-populations. The post-EMT CSCs that possess plasticity exhibit particularly enhanced therapeutic resistance and are defined by a CD44highEpCAMlow/-CD24+ cell surface marker profile. Treatment with TGFβ and retinoic acid (RA) enabled enrichment of this sub-population for therapeutic testing, through which the endoplasmic reticulum (ER) stressor and autophagy inhibitor Thapsigargin was shown to selectively target these cells. Demonstration of the link between phenotypic plasticity and therapeutic resistance, and development of an in vitro method for enrichment of a highly resistant CSC sub-population, provides an opportunity for the development of improved chemotherapeutic agents that can eliminate CSCs.

2016-01-12 | GSE74580 | GEO

Phenotypic plasticity determines cancer stem cell therapeutic resistance in oral squamous cell carcinoma I

Project description:Cancer stem cells (CSCs) drive tumour spread and therapeutic resistance, and can undergo epithelial-to-mesenchymal transition (EMT) and mesenchymal-to-epithelial transition (MET) to switch between epithelial and post-EMT sub-populations. Examining oral squamous cell carcinoma (OSCC), we now show that increased phenotypic plasticity, the ability to undergo EMT/MET, underlies increased CSC therapeutic resistance within both the epithelial and post-EMT sub-populations. The post-EMT CSCs that possess plasticity exhibit particularly enhanced therapeutic resistance and are defined by a CD44highEpCAMlow/-CD24+ cell surface marker profile. Treatment with TGFβ and retinoic acid (RA) enabled enrichment of this sub-population for therapeutic testing, through which the endoplasmic reticulum (ER) stressor and autophagy inhibitor Thapsigargin was shown to selectively target these cells. Demonstration of the link between phenotypic plasticity and therapeutic resistance, and development of an in vitro method for enrichment of a highly resistant CSC sub-population, provides an opportunity for the development of improved chemotherapeutic agents that can eliminate CSCs.

2016-01-12 | GSE74578 | GEO

Phenotypic plasticity determines cancer stem cell therapeutic resistance in oral squamous cell carcinoma II

Project description:Cancer stem cells (CSCs) drive tumour spread and therapeutic resistance, and can undergo epithelial-to-mesenchymal transition (EMT) and mesenchymal-to-epithelial transition (MET) to switch between epithelial and post-EMT sub-populations. Examining oral squamous cell carcinoma (OSCC), we now show that increased phenotypic plasticity, the ability to undergo EMT/MET, underlies increased CSC therapeutic resistance within both the epithelial and post-EMT sub-populations. The post-EMT CSCs that possess plasticity exhibit particularly enhanced therapeutic resistance and are defined by a CD44highEpCAMlow/-CD24+ cell surface marker profile. Treatment with TGFÎ² and retinoic acid (RA) enabled enrichment of this sub-population for therapeutic testing, through which the endoplasmic reticulum (ER) stressor and autophagy inhibitor Thapsigargin was shown to selectively target these cells. Demonstration of the link between phenotypic plasticity and therapeutic resistance, and development of an in vitro method for enrichment of a highly resistant CSC sub-population, provides an opportunity for the development of improved chemotherapeutic agents that can eliminate CSCs. The clonal derivative of the CA1 OSCC cell line termed 18 here (otherwise termed pEMT-P) was treated with 0.5ng/ml TGFbeta and/or 5uM RA for eight days, with media changed every second day. The LM OSCC cell line was FACS sorted to recover the CD44highEpCAMlowCD24+ sub-population, which was then treated with 0.5ng/ml TGFbeta and/or 5uM RA for eight days, with media changed every second day. The parental CA1 and LM cell lines are included as reference samples.

2016-01-12 | E-GEOD-74580 | biostudies-arrayexpress

Type I IFNs promote cancer cell stemness by triggering the epigenetic regulator KDM1B

Project description:Cancer stem cells (CSCs) are immature, immortal cells within tumors, adept at resisting therapeutic pressure and responsible for local and distant disease recurrence. Non-genetic mechanisms of acquired resistance are increasingly being described, however molecular insights into this evolutionary process still lack. Here, we showed that Type I interferons (IFNs-I) act as molecular hubs of resistance during immunogenic chemotherapy, as they trigger the epigenetic regulator KDM1B, responsible for an adaptive, yet reversible, transcriptional rewiring of cancer cells towards stemness and immune escape. Accordingly, KDM1B pharmacological inhibition antagonizes the appearance of IFN-I-adapted CSCs, both in vitro and in vivo. Notably, IFN-I-adapted CSCs are heterogeneous in terms of multidrug resistance, plasticity, invasiveness and immunogenicity. Moreover, in breast cancer patients receiving anthracycline-based chemotherapy, IFN-I and KDM1B signatures positively correlate with CSC and immune evasion markers. Our study identifies IFN-I→KDM1B axis as a potent engine of cancer cell reprogramming and recommends KDM1B targeting an attractive adjunctive to immunogenic drugs to prevent CSC expansion and increase the long-term benefit of therapy.

2022-06-30 | GSE173851 | GEO

Expression data of GFP-high or low cells of LGR5-GFP or KRT20-GFP knock-in human colorectal tumor organoids.

Project description:We analyzed gene expression of 3 lines LGR5-GFP, 2 lines KRT20-GFP knock-in colorectal tumor organdies. The cancer stem cell (CSC) theory highlights a self-renewing subpopulation of cancer cells that fuels tumour growth. The existence of human CSCs is mainly supported by xenotransplantation of prospectively isolated cells, but their clonal dynamics and plasticity remain unclear. Here, we show that human LGR5+ colorectal cancer cells serve as CSCs in growing cancer tissues. Lineage-tracing experiments with a tamoxifen inducible Cre knock-in allele of LGR5 reveal the self-renewal and differentiation capacity of LGR5+ tumour cells. Selective ablation of LGR5+ CSCs in LGR5-iCaspase9 knock-in organoids leads to tumour regression, followed by tumour regrowth driven by re-emerging LGR5+ CSCs. KRT20 knock-in reporter marks differentiated cancer cells that constantly diminish in tumour tissues, while reverting to LGR5+ CSCs and contributing to tumour regrowth after LGR5+ CSC ablation. We also show that combined chemotherapy potentiates LGR5+ CSCs targeting. These data provide insights into the plasticity of CSCs and their potential as a therapeutic target in human colorectal cancer.

2017-03-30 | GSE83513 | GEO

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