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| Status |
Public on Apr 24, 2022 |
| Title |
Localization of a TORC1-eIF4F translation complex during CD8+ T cell activation drives divergent cell fate |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Activated CD8+ T lymphocytes differentiate into heterogeneous subsets. Using super-resolution imaging, we found that prior to the first division, dynein-dependent vesicular transport polarized active TORC1 towards the microtubule-organizing center (MTOC) at the proximal pole. This active TORC1 was physically associated with active eIF4F, required for the translation of c-myc mRNA. As a consequence, c-myc translating polysomes polarized toward the cellular pole proximal to the immune synapse, resulting in localized c-myc translation. Upon division, the TORC1-eIF4A complex preferentially sorted to the proximal daughter cell, facilitating asymmetric c-Myc synthesis. Transient disruption of eIF4A activity at first division skewed long-term cell fate trajectories to memory-like function. Using a genetic barcoding approach, we found that first-division sister cells often displayed differences in transcriptional profiles that largely correlated with c-Myc and TORC1 target genes. Our findings provide mechanistic insights as to how distinct T cell fate trajectories can be established during the first division.
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| Overall design |
CTV-labeled GFP-c-Myc OT-I CD8+ T cells were activated on peptide-pulsed APCs for 36 h. First-division GFP-c-Mychigh and GFP-c-Myclow cell populations (CD8+, CTV 2nd peak, highest and lowest 20% GFP-c-Myc) were sorted into medium with or without 200 nM Silvestrol and cultured for additional 2 h.
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| Contributor(s) |
Liedmann S, Guo A, Chen MJ, Green DR |
| Citation(s) |
35597236 |
| NIH grant(s) |
| Grant ID |
Grant title |
Affiliation |
Name |
| P30 CA021765 |
Cancer Center Support Grant (CCSG) |
ST. JUDE CHILDREN'S RESEARCH HOSPITAL |
CHARLES ROBERTS |
| R01 AI123322 |
Establishment, maintenance, and consequences of asymmetric cell division in T cells |
ST. JUDE CHILDREN'S RESEARCH HOSPITAL |
DOUGLAS R GREEN |
| R01 AI123322 |
Establishment, maintenance, and consequences of asymmetric cell division in T cells |
ST. JUDE CHILDREN'S RESEARCH HOSPITAL |
DOUGLAS R GREEN |
| R01 AI123322 |
Establishment, maintenance, and consequences of asymmetric cell division in T cells |
ST. JUDE CHILDREN'S RESEARCH HOSPITAL |
DOUGLAS R GREEN |
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| Submission date |
Feb 17, 2022 |
| Last update date |
Jul 24, 2022 |
| Contact name |
Douglas R Green |
| E-mail(s) |
douglas.green@stjude.org
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| Organization name |
St Jude Children's Research Hospital
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| Department |
Immunology
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| Lab |
Green lab
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| Street address |
262 Danny Thomas Pl
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| City |
Memphis |
| State/province |
United States |
| ZIP/Postal code |
38105 |
| Country |
USA |
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| Platforms (1) |
| GPL21103 |
Illumina HiSeq 4000 (Mus musculus) |
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| Samples (2) |
| GSM5905909 |
Myc binding, control, replicate 1 |
| GSM5905910 |
Myc binding, silvestrol-treated, replicate 1 |
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| Relations |
| BioProject |
PRJNA808088 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE196967_RAW.tar |
235.4 Mb |
(http)(custom) |
TAR (of BED, BIGWIG) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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