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Series GSE248856 Query DataSets for GSE248856
Status Public on Dec 01, 2023
Title Transcriptomic Analysis Identifies B-Lymphocyte Kinase as a Therapeutic Target for Desmoplastic Small Round Cell Tumor Cancer Stem Cell-Like Cells [scRNA-seq]
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Desmoplastic Small Round Cell Tumor (DSRCT) is an aggressive pediatric cancer caused by the EWSR1-WT1 fusion oncoprotein. The tumor is refractory to treatment with a 5-year survival rate of only 15-25%, necessitating the development of novel therapeutics, especially those able to target chemoresistant subpopulations. Novel in vitro cancer stem cell-like (CSC-like) culture conditions increase the expression of stemness markers (SOX2, NANOG) and reduce DSRCT cell line susceptibility to chemotherapy, while maintaining the ability of DSRCT cells to form xenografts. To gain insights into this chemoresistant model, RNA-seq was performed to elucidate transcriptional alterations between DSRCT cells grown in CSC-like spheres and normal 2-dimensional adherent state. Commonly upregulated and downregulated genes were identified and utilized in pathway analysis revealing upregulation of pathways related to chromatin assembly and disassembly and downregulation of pathways including cell junction assembly and extracellular matrix organization. Alterations in chromatin assembly suggest a role for epigenetics in the DSRCT CSC-like state which was further investigated with ATAC-seq, identifying over 10,000 differentially accessible peaks including 4,444 sphere accessible peaks and 6,120 adherent accessible peaks. Accessible regions were associated with higher gene expression including increased accessibility of the CSC marker SOX2 in CSC-like culture conditions. These analyses were further utilized to identify potential CSC therapeutic targets, leading to the identification of B-lymphocyte kinase (BLK) as a CSC-enriched, EWSR1-WT1 regulated, druggable target. BLK inhibition and knockdown reduced CSC-like properties including abrogation of tumorsphere formation and stemness marker expression. Importantly, BLK knockdown reduced DSRCT CSC-like cell chemoresistance making its inhibition a promising target for future combination therapy.
 
Overall design DSRCT cell lines were cultured in sphere or adherent culture conditions for 4-days and then harvested for analysis by RNA-seq (JN-DSRCT-1, BER-DSRCT, BOD-DSRCT), ATAC-seq (BER-DSRCT), or scRNA-seq (JN-DSRCT-1, BER-DSRCT).
 
Contributor(s) Lee SB, Magrath JW
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Submission date Nov 28, 2023
Last update date Dec 01, 2023
Contact name Sean Bong Lee
E-mail(s) slee30@tulane.edu
Organization name Tulane University School of Medicine
Department Pathology
Lab Lee Lab
Street address 1700 Tulane Ave
City New Orleans
State/province LA
ZIP/Postal code 70112
Country USA
 
Platforms (1)
GPL24676 Illumina NovaSeq 6000 (Homo sapiens)
Samples (2)
GSM7921345 Multiplexed sample (JN-DSRCT-1 Adherent, JN-DSRCT-1 Sphere, BER-DSRCT Adherent, BER-DSRCT Sphere), GEX
GSM7921346 Multiplexed sample (JN-DSRCT-1 Adherent, JN-DSRCT-1 Sphere, BER-DSRCT Adherent, BER-DSRCT Sphere), CMO
This SubSeries is part of SuperSeries:
GSE248857 Transcriptomic Analysis Identifies B-Lymphocyte Kinase as a Therapeutic Target for Desmoplastic Small Round Cell Tumor Cancer Stem Cell-Like Cells
Relations
BioProject PRJNA1046116

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Supplementary file Size Download File type/resource
GSE248856_BER_A_filtered_barcodes.csv.gz 10.9 Kb (ftp)(http) CSV
GSE248856_BER_A_filtered_feature_bc_matrix.h5 19.3 Mb (ftp)(http) H5
GSE248856_BER_S_filtered_barcodes.csv.gz 10.5 Kb (ftp)(http) CSV
GSE248856_BER_S_filtered_feature_bc_matrix.h5 14.0 Mb (ftp)(http) H5
GSE248856_CMO_details_README.txt 126 b (ftp)(http) TXT
GSE248856_JN_A_filtered_barcodes.csv.gz 12.5 Kb (ftp)(http) CSV
GSE248856_JN_A_filtered_feature_bc_matrix.h5 20.4 Mb (ftp)(http) H5
GSE248856_JN_S_filtered_barcodes.csv.gz 10.3 Kb (ftp)(http) CSV
GSE248856_JN_S_filtered_feature_bc_matrix.h5 13.2 Mb (ftp)(http) H5
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