| Accession |
PRJCA010549 |
| Title |
USP7 modulates K63 polyubiquitination of mTOR, which is essential for human pluripotent stem cell function |
| Relevance |
Medical |
| Data types |
Transcriptome or Gene expression
Raw sequence reads
|
| Organisms |
Homo sapiens
|
| Description |
Finely tuned translational control has been shown to regulate cell fate decisions rather than just perform a housekeeping function. However, how protein synthesis is controlled to impact stem cell function remains poorly understood. Here, we reveal that USP7, a deubiquitinase, directly modulates mTOR activity, the key driver of protein synthesis, in human embryonic stem cells (hESCs) and is essential for hESC function. USP7 directly modulates mTOR activity through K63-linked polyubiquitination. USP7-/- hESCs exhibit elevated ribosome assembly and protein synthesis, which impairs their fate specification into the three embryonic germ layers. Furthermore, we reveal an immediate downregulation of K63-linked polyubiquitination and protein synthesis prior to transcriptional changes at early differentiation onset in hESCs. Finally, we demonstrate the essential role of USP7 in regulating the translational switch during pluripotency exit. In summary, we identify USP7 and its noncanonical K63-linked polyubiquitination as a novel cell-intrinsic translational control mechanism essential for stem cell function. |
| Sample scope |
Monoisolate |
| Release date |
2024-07-16 |
| Grants |
| Agency |
program |
Grant ID |
Grant title |
| Ministry of Science and Technology of the People's Republic of China (MOST)
|
|
2017YFA0102600
|
|
|
|
| Submitter |
Guangjin
Pan (pan_guangjin@gibh.ac.cn)
|
| Organization |
Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences |
| Submission date |
2022-07-16 |
