Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Chi3l1 is a modulator of glioma stem cell states and a therapeutic vulnerability for glioblastoma

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE184698 | GEO | 2022/10/24

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Chi3l1 Is a Modulator of Glioma Stem Cell States and a Therapeutic Target in Glioblastoma.

Project description:Chitinase 3-like 1 (Chi3l1) is a secreted protein that is highly expressed in glioblastoma. Here, we show that Chi3l1 alters the state of glioma stem cells (GSC) to support tumor growth. Exposure of patient-derived GSCs to Chi3l1 reduced the frequency of CD133+SOX2+ cells and increased the CD44+Chi3l1+ cells. Chi3l1 bound to CD44 and induced phosphorylation and nuclear translocation of β-catenin, Akt, and STAT3. Single-cell RNA sequencing and RNA velocity following incubation of GSCs with Chi3l1 showed significant changes in GSC state dynamics driving GSCs towards a mesenchymal expression profile and reducing transition probabilities towards terminal cellular states. ATAC-seq revealed that Chi3l1 increases accessibility of promoters containing a Myc-associated zinc finger protein (MAZ) transcription factor footprint. Inhibition of MAZ downregulated a set of genes with high expression in cellular clusters that exhibit significant cell state transitions after treatment with Chi3l1, and MAZ deficiency rescued the Chi3L-induced increase of GSC self-renewal. Finally, targeting Chi3l1 in vivo with a blocking antibody inhibited tumor growth and increased the probability of survival. Overall, this work suggests that Chi3l1 interacts with CD44 on the surface of GSCs to induce Akt/β-catenin signaling and MAZ transcriptional activity, which in turn upregulates CD44 expression in a pro-mesenchymal feed-forward loop. The role of Chi3l1 in regulating cellular plasticity confers a targetable vulnerability to glioblastoma.SignificanceChi3l1 is a modulator of glioma stem cell states that can be targeted to promote differentiation and suppress growth of glioblastoma.

| S-EPMC10267676 | biostudies-literature

Chi3l1 is a modulator of glioma stem cell states and a therapeutic vulnerability for glioblastoma [scRNA-seq]

Project description:Chi3l1 (Chitinase 3-like 1) is a secreted protein highly expressed in glioblastoma. Here, we show that exposure of glioma stem cells (GSCs) to Chi3l1 reduces the CD133+/SOX2+ cells and increases the CD44+/Chi3l1+ cells. Single cell RNA-seq and RNA velocity following incubation of GSCs with Chi3l1 show significant changes in GSC state dynamics driving GSCs towards a mesenchymal expression profile and reducing transition probabilities towards terminal cellular states. ATAC-seq reveals that Chi3l1 increases accessibility of promoters containing MAZ transcription factor footprint. Inhibition of MAZ directly regulates genes with highest expression in cellular clusters exhibiting significant cell state transitions.

2022-10-24 | GSE184696 | GEO

Chi3l1 is a modulator of glioma stem cell states and a therapeutic vulnerability for glioblastoma [RNA-seq]

2022-10-24 | GSE184695 | GEO

Chi3l1 is a modulator of glioma stem cell states and a therapeutic vulnerability for glioblastoma

Project description:Chi3l1 is a modulator of glioma stem cell states and a therapeutic vulnerability for glioblastoma

| PRJNA765679 | ENA

Chi3l1 is a modulator of glioma stem cell states and a therapeutic vulnerability for glioblastoma [RNA-seq]

Project description:Chi3l1 is a modulator of glioma stem cell states and a therapeutic vulnerability for glioblastoma [RNA-seq]

| PRJNA765690 | ENA

Chi3l1 is a modulator of glioma stem cell states and a therapeutic vulnerability for glioblastoma [scRNA-seq]

Project description:Chi3l1 is a modulator of glioma stem cell states and a therapeutic vulnerability for glioblastoma [scRNA-seq]

| PRJNA765691 | ENA

A Transcriptional State Driven by Yin Yang 1 Confers a Therapeutic Vulnerability in Glioblastoma Stem Cells

Project description:This SuperSeries is composed of the SubSeries listed below.

2022-06-01 | GSE155839 | GEO

Chromatin states and Transcriptome in in glioblastoma stem cells

Project description:This SuperSeries is composed of the SubSeries listed below.

2021-03-09 | GSE161440 | GEO

Aberrant differentiation of glioma stem cells: Implications for therapeutic targeting

Project description:This SuperSeries is composed of the SubSeries listed below.

2015-09-01 | GSE58924 | GEO

Antibody blockade resets CHI3L1-induced glioma stem cell phenotypic transitions and reduces glioblastoma tumor burden

Project description:CHI3L1 (Chitinase 3-like1) is one of the highest expressed genes in glioblastoma and is associated with therapy resistance and low survival of patients. Here, we show that exposure of glioma stem cells (GSCs) to CHI3L1 induces marked phenotypic and transcriptomic change from CD133+/SOX2+ pro-neural to CD44+/CHI3L1+ mesenchymal phenotype. CHI3L1 induces chromatin remodeling in GSCs and regulates accessibility of ZNF281, CTCFL, SOX9, and the OCT4-SOX2-TCF3-NANOG transcription factor complex that drive the CHI3L1-mediated mesenchymal “switch” and maintain GSC identity.

2022-10-24 | GSE154060 | 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