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Series GSE140441 Query DataSets for GSE140441
Status Public on May 05, 2021
Title EGFR/FOXO3a/BIM signalling pathway determines chemosensitivity of BMP4-differentiated glioma stem cells to temozolomide
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Accumulating evidence suggests that glioma stem cells (GSCs), rare cells characterised by pluripotency and self-renewal, are responsible for glioblastoma (GBM) propagation, recurrence and resistance to therapy. Differentiation with bone morphogenic proteins (BMPs) is considered to be a promising approach to eliminate GSCs and sensitise glioma to chemotherapeutics. Epidermal growth factor receptor (EGFR) gene alterations are detected in more than a half of GBMs, however, the role of EGFR in chemoresistance of glioma stem cells remain elusive. Here, we investigated whether EGFR signalling affects BMP4-induced differentiation of GSCs and their response to an alkylating drug temozolomide (TMZ). We show that BMP4 triggers Smad signalling cascade in glioma stem cells independently of the EGFR level. BMP4 down-regulated levels of pluripotency markers (SOX2 and OLIG2) with the concomitant induction of astrocytic (GFAP) and neuronal (b-Tubulin III) markers. However, significant differences in chemotherapy outcomes were observed in glioma stem cells with different EGFR levels. BMP4-induced differentiation did not enhance sensitivity to TMZ in EGFRlow GSCs, in contrast to EGFRhigh GSCs, which were undergoing apoptosis. We identified differences in cell cycle regulation by analyses of cell cycle phase distribution and cell-cycle-related proteins. In cells with lower EGFR expression BMP4 triggered the G1 cell cycle arrest, not detected in EGFRhigh cells. RNA-seq profiles further highlighted transcriptomic alternations and distinct processes characterizing EGFR-dependent responses in course of BMP4-induced differentiation. We identified AKT/FOXO3a axis controlling of BIM (the pro-apoptotic BCL-2 family protein) as operating only in EGFRhigh BMP4-differentiated and TMZ-treated cells.
Overall design Examination of BMP4-triggered differentiation of glioma stem cells with regard to EGFR signaling
Contributor(s) Ciechomska IA, Gielniewski B, Wojtas B, Kaminska B, Mieczkowski J
Citation(s) 32788653
Submission date Nov 15, 2019
Last update date May 05, 2021
Contact name Jakub Mieczkowski
Organization name Medical University of Gdansk
Street address Debinki 12
City Gdansk
ZIP/Postal code 80-211
Country Poland
Platforms (1)
GPL18460 Illumina HiSeq 1500 (Homo sapiens)
Samples (12)
GSM4161776 L0125_UNT_rep1_RNAseq
GSM4161777 L0125_UNT_rep2_RNAseq
GSM4161778 L0125_TMZ_RNAseq
BioProject PRJNA589752
SRA SRP230182

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE140441_RAW.tar 2.4 Gb (http)(custom) TAR (of BEDGRAPH)
GSE140441_expression.matrix.tsv.gz 1.5 Mb (ftp)(http) TSV
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file
Processed data are available on Series record

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