Summary of project PR001347
This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR001347. The data can be accessed directly via it's Project DOI: 10.21228/M8M417 This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Project ID: | PR001347 |
| Project DOI: | doi: 10.21228/M8M417 |
| Project Title: | GCN2 deletion influenced the energy metabolism in HSPCs. |
| Project Summary: | Hematopoietic stem cells (HSCs) adapt their metabolism to maintenance and proliferation, but the mechanism remains incompletely understood. Here, we demonstrated that homeostatic HSCs had high amino acid (AA) catabolism to reduce the cellular AA levels, which activated the GCN2-eIF2α axis, a protein-synthesis-inhibitory checkpoint to inhibit protein synthesis for maintenance. Furthermore, upon proliferation conditions, HSCs increased mitochondrial oxidative phosphorylation (OXPHOS) for higher energy production but decreased AA catabolism to accumulate cellular AAs, which inactivated the GCN2-eIF2α axis to increase protein synthesis and coupled with proteotoxic stress. Importantly, GCN2 deletion impaired HSC function in repopulation and regeneration. Mechanistically, GCN2 maintained proteostasis and inhibited Src mediated AKT activation to repress mitochondrial OXPHOS in HSCs. Moreover, glycolytic metabolite, NAD+ precursor nicotinamide riboside (NR), accelerated AA catabolism to activate GCN2 and sustain long-term function of HSCs. Overall, our study uncovers the direct links between metabolic alterations and translation control in HSCs during homeostasis and proliferation. |
| Institute: | Sun Yat-sen University |
| Last Name: | Zhao |
| First Name: | Meng |
| Address: | Zhongshan 2nd Road |
| Email: | zhaom38@mail.sysu.edu.cn |
| Phone: | 18138799889 |
Summary of all studies in project PR001347
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST002123 | GCN2 regulates mitochondrial OXPHOS in HSPCs under proliferation conditions. | Mus musculus | Sun Yat-sen University | MS | 2022-11-01 | 1 | 12 | Uploaded data (1.3M)* |
