|
| Status |
Public on Jan 14, 2021 |
| Title |
Satellite cell expansion is mediated by P-eIF2α-dependent Tacc3 translation |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Translational control of gene expression is an important regulator of adult stem cell quiescence, activation and self-renewal. In skeletal muscle, quiescent satellite cells maintain low levels of protein synthesis, mediated in part through the phosphorylation of eIF2α (P-eIF2α). Pharmacological inhibition of the eIF2α phosphatase with the small molecule sal003 maintains P-eIF2α and permits the expansion of satellite cells ex vivo. Paradoxically, P-eIF2α also increases the translation of specific mRNAs, which is mediated by P-eIF2α-dependent read-through of inhibitory upstream open reading frames (uORFs). Here, we ask whether P-eIF2α-dependent mRNA translation enables expansion of satellite cells. Using transcriptomic and proteomic analyses, we show a number of genes associated with the assembly of the spindle pole to be upregulated at the level of protein, without corresponding change in mRNA levels, in satellite cells expanded in the presence of sal003. We show that uORFs in the 5′ UTR of mRNA for the mitotic spindle stability gene Tacc3 direct P-eIF2α-dependent translation. Satellite cells deficient for TACC3 exhibit defects in expansion, self-renewal and regeneration of skeletal muscle.
|
| |
|
| Overall design |
Satellite cells of adult Pax3GFP/+ mice after 4-day culture in presence of 10 μM sal003 (4 replicates) or under normal conditions (DMSO, 4 replicates) for a total of 8 samples.
|
| |
|
| Contributor(s) |
Fujita R, Jamet S, Lean G, Cheng HM, Hébert S, Kleinman CL, Crist C |
| Citation(s) |
33318147 |
| |
| Submission date |
Jan 13, 2021 |
| Last update date |
Apr 15, 2021 |
| Contact name |
Claudia L Kleinman |
| E-mail(s) |
[email protected]
|
| Phone |
514-340-8222 25139
|
| Organization name |
Lady Davis Institute for Medical Research
|
| Department |
Human Genetics
|
| Street address |
3999 Côte Ste-Catherine Road
|
| City |
Montréal |
| State/province |
Québec |
| ZIP/Postal code |
H3T 1E2 |
| Country |
Canada |
| |
|
| Platforms (1) |
|
| Samples (8)
|
|
| Relations |
| BioProject |
PRJNA691923 |
| SRA |
SRP301616 |
Less...
More...