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GEO help: Mouse over screen elements for information. |
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Status |
Public on Jun 15, 2022 |
Title |
Synergistic function screening of multiple checkpoint perturbation in TIL |
Organism |
Mus musculus |
Experiment type |
Other
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Summary |
A synergistic function screening system was established, in which a multiplexed CRIPSR knockout library targeting different checkpoint combinations was constructed and transduced into CD8+T cells to block multiple checkpoints in single cell. Based on this system, we performed a in vivo synergistic function screening of several checkpoints in tumor infiltrating CD8+T cells and find the best combined checkpoint blockade strategy to boost the CD8+T cell-mediated tumor elimination in vivo.
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Overall design |
In the library designing, a total of 6 checkpoints PDCD1, CTLA4, TIGIT, BTLA, TIM3 and A2AR were selected to make a total of 56 combinations (Table 1). Meanwhile, two distinct biological control groups were created. One group contained 30 combinations covering 5 co-stimulatory molecules for T cell activation, another one contained 15 combinations covering 4 critical molecules in TCR signaling. 6 groups of sgRNA were designed against individual combination. In each combination that contained less than 4 targeting sgRNAs, the non-targeting sgRNAs were included as the patch. At last, a total of 84 non-targeting 4-sgRNA combinations were included as the negative control.
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Contributor(s) |
Lu Z, Ni K, Wang Y, Ma L |
Citation(s) |
35670669 |
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Submission date |
May 10, 2022 |
Last update date |
Jul 07, 2022 |
Contact name |
Lijia Ma |
E-mail(s) |
malabdata@westlake.edu.cn
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Organization name |
Westlake university
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Department |
School of Life Sciences
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Lab |
Lijia Ma
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Street address |
Shilongshan Road No.18, Cloud Town, Xihu District
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City |
Hangzhou |
State/province |
Zhejiang |
ZIP/Postal code |
310024 |
Country |
China |
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Platforms (1) |
GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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Samples (12)
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GSM6127804 |
SR-rep2-gRNA2gRNA3 [mTcell.CP.SR2.G23] |
GSM6127805 |
SR-rep3-gRNA1gRNA2 [mTcell.CP.SR3.G12] |
GSM6127806 |
SR-rep3-gRNA2gRNA3 [mTcell.CP.SR3.G23] |
GSM6127807 |
TIL-rep1-gRNA1gRNA2 [mTcell.CP.T1.G12] |
GSM6127808 |
TIL-rep1-gRNA2gRNA3 [mTcell.CP.T1.G23] |
GSM6127809 |
TIL-rep2-gRNA1gRNA2 [mTcell.CP.TA1.G12] |
GSM6127810 |
TIL-rep2-gRNA2gRNA3 [mTcell.CP.TA1.G23] |
GSM6127811 |
TIL-rep3-gRNA1gRNA2 [mTcell.CP.TA3.G12] |
GSM6127812 |
TIL-rep3-gRNA2gRNA3 [mTcell.CP.TA3.G23] |
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Relations |
BioProject |
PRJNA836888 |
Supplementary file |
Size |
Download |
File type/resource |
GSE202653_Hepa1-6_InVivoScreen.xlsx |
167.8 Kb |
(ftp)(http) |
XLSX |
SRA Run Selector |
Raw data are available in SRA |
Processed data are available on Series record |
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