|
| Status |
Public on Nov 02, 2022 |
| Title |
Genome-wide CRISPR screen reveals a key role for integrin avb3 in TH2 cell polarisation [RNA-seq I] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
T helper 2 (TH2) cells play critical roles in protective immunity against parasitic helminth infections and in tissue repair. However, misdirected TH2 cell responses promote allergy and asthma. Using whole-genome CRISPR-Cas9 screens in developing TH2 cells we defined a functional TH2ome for TH2 differentiation and validated a diverse array of molecules not previously linked to TH2 cell development and function. Strikingly, we discovered that integrin avb3 plays a key and previously unappreciated role in the differential polarisation of TH2 cells and their type 2 cytokine expression. Conversely, we did not identify the LFA-1 integrin which mediates inside-out signalling following TCR ligation as part of the T cell synapse and preferentially promotes TH1 differentiation. We find that TH2 cell expression of integrin avb3 is required for the formation of TH2 cell clusters that exhibit enhanced T cell activation, promoting proliferation and TH2 cell differentiation, and thereby potentiating antigen-driven TH2 cell responses.
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| Overall design |
Transcriptomic analyses of sorted T helper cell populations with CRISPR- or flox mediated knockout.
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| Contributor(s) |
Szeto AC, Ferreira AC, Mannion J, Clark PA, Sivasubramaniam M, Heycock MW, Crisp A, Jolin HE, Kozik P, McKenzie AN |
| Citation(s) |
36550322 |
| |
| Submission date |
Jun 30, 2021 |
| Last update date |
Jan 13, 2023 |
| Contact name |
Alastair Crisp |
| Organization name |
MRC Laboratory of Molecular Biology
|
| Street address |
Francis Crick Avenue
|
| City |
Cambridge |
| ZIP/Postal code |
CB2 0QH |
| Country |
United Kingdom |
| |
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| Platforms (1) |
| GPL21103 |
Illumina HiSeq 4000 (Mus musculus) |
|
| Samples (9)
|
| GSM5411482 |
Nontargeting_sgRNA_Tomneg_replicate1 [S1] |
| GSM5411483 |
Nontargeting_sgRNA_Tomneg_replicate2 [S2] |
| GSM5411484 |
Nontargeting_sgRNA_Tomneg_replicate3 [S5] |
| GSM5411485 |
Nontargeting_sgRNA_Tompos_replicate1 [S6] |
| GSM5411486 |
Nontargeting_sgRNA_Tompos_replicate2 [S7] |
| GSM5411487 |
Nontargeting_sgRNA_Tompos_replicate3 [S10] |
| GSM5411488 |
Gata3_sgRNA_Tomneg_replicate1 [S11] |
| GSM5411489 |
Gata3_sgRNA_Tomneg_replicate2 [S12] |
| GSM5411490 |
Gata3_sgRNA_Tomneg_replicate3 [S15] |
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| This SubSeries is part of SuperSeries: |
| GSE179210 |
Genome-wide CRISPR screen reveals a key role for integrin avb3 in TH2 cell polarisation. |
|
| Relations |
| BioProject |
PRJNA742702 |
| SRA |
SRP326320 |
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