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GEO help: Mouse over screen elements for information. |
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| 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
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| 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.
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| Overall design |
CD45+CD11b+Ly6Chi were sorted from MC38 tumors or blood of MC38 tumor-bearing mice and analyzed using scRNA-seq.
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| Contributor(s) |
Wang L, Dou X, Liang HL, He C, Weichselbaum RR |
| Citation(s) |
37236197 |
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| Submission date |
Jun 17, 2022 |
| Last update date |
Jul 28, 2023 |
| Contact name |
Xiaoyang Dou |
| E-mail(s) |
xiaoyang.dou@sibcb.ac.cn
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| Organization name |
CAS Center for Excellence in Molecular Cell Science, CAS
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| Street address |
320 Yue Yang Road
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| City |
Shanghai |
| ZIP/Postal code |
200031 |
| Country |
China |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (8)
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| GSM6252829 |
Tumor, IR, HTO-derived cDNA |
| GSM6252830 |
Blood, Control, mRNA-derived cDNA |
| GSM6252831 |
Blood, Control, HTO-derived cDNA |
| GSM6252832 |
Blood, IR, mRNA-derived cDNA |
| GSM6252833 |
Blood, IR, HTO-derived cDNA |
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| This SubSeries is part of SuperSeries: |
| GSE206387 |
YTHDF2 inhibition potentiates radiotherapy by reprogramming suppressive myeloid cells |
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| Relations |
| BioProject |
PRJNA850409 |
| 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 |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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