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Series GSE206381 Query DataSets for GSE206381
Status Public on Apr 28, 2023
Title YTHDF2 inhibition potentiates radiotherapy by reprogramming suppressive myeloid cells [CITE-Seq]
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary RNA N6-methyladenosine (m6A) modification is implicated in cancer progression. However, the impact of m6A on the antitumor effects of radiotherapy and the related mechanisms are unknown. Here we show that ionizing radiation (IR) induces immunosuppressive myeloid-derived suppressor cell (MDSC) expansion and YTHDF2 expression in both murine models and humans. Following IR, loss of Ythdf2 in myeloid cells augments antitumor immunity and overcomes tumor radioresistance by altering MDSC differentiation and inhibiting MDSC infiltration and suppressive function. The remodeling of the landscape of MDSC populations by local IR is reversed by Ythdf2 deficiency. IR-induced YTHDF2 expression relies on NF-κB signaling; YTHDF2 in turn leads to NF-κB activation by directly binding and degrading transcripts encoding negative regulators of NF-κB signaling, resulting in an IR-YTHDF2-NF-κB circuit. Pharmacological inhibition of YTHDF2 overcomes MDSC-induced immunosuppression and improves combined IR and/or anti-PD-L1 treatment. Thus, YTHDF2 is a promising target to improve radiotherapy (RT) and RT/immunotherapy combinations.
 
Overall design CD45+CD11b+Ly6Chi were sorted from MC38 tumors or blood of MC38 tumor-bearing mice and analyzed using scRNA-seq.
 
Contributor(s) Wang L, Dou X, Liang HL, He C, Weichselbaum RR
Citation(s) 37236197
Submission date Jun 17, 2022
Last update date Jul 28, 2023
Contact name Xiaoyang Dou
E-mail(s) xiaoyang.dou@sibcb.ac.cn
Organization name CAS Center for Excellence in Molecular Cell Science, CAS
Street address 320 Yue Yang Road
City Shanghai
ZIP/Postal code 200031
Country China
 
Platforms (1)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (8)
GSM6252826 Tumor, Control, mRNA-derived cDNA
GSM6252827 Tumor, Control, HTO-derived cDNA
GSM6252828 Tumor, IR, mRNA-derived cDNA
This SubSeries is part of SuperSeries:
GSE206387 YTHDF2 inhibition potentiates radiotherapy by reprogramming suppressive myeloid cells
Relations
BioProject PRJNA850409

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

Supplementary file Size Download File type/resource
GSE206381_RRW-01-barcodes.tsv.gz 5.7 Mb (ftp)(http) TSV
GSE206381_RRW-01-features.tsv.gz 254.1 Kb (ftp)(http) TSV
GSE206381_RRW-01-matrix.mtx.gz 121.5 Mb (ftp)(http) MTX
GSE206381_RRW-02-barcodes.tsv.gz 5.8 Mb (ftp)(http) TSV
GSE206381_RRW-02-features.tsv.gz 254.1 Kb (ftp)(http) TSV
GSE206381_RRW-02-matrix.mtx.gz 119.1 Mb (ftp)(http) MTX
GSE206381_RRW-03-barcodes.tsv.gz 4.1 Mb (ftp)(http) TSV
GSE206381_RRW-03-features.tsv.gz 254.1 Kb (ftp)(http) TSV
GSE206381_RRW-03-matrix.mtx.gz 74.1 Mb (ftp)(http) MTX
GSE206381_RRW-04-barcodes.tsv.gz 4.2 Mb (ftp)(http) TSV
GSE206381_RRW-04-features.tsv.gz 254.1 Kb (ftp)(http) TSV
GSE206381_RRW-04-matrix.mtx.gz 72.3 Mb (ftp)(http) MTX
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