| Accession |
PRJCA004493 |
| Title |
APOE triggers cellular senescence via disturbing nuclear envelope homeostasis |
| Relevance |
Medical |
| Data types |
Whole genome sequencing
Epigenomics
Raw sequence reads
Genome sequencing
|
| Organisms |
Homo sapiens
|
| Description |
Apolipoprotein E (APOE) is one of the main cholesterol transporters involved in the maintenance of cholesterol metabolism and is closely related to human lifespan. However, it remains largely unknown how APOE regulates human stem cell senescence. Here, we found that APOE expression was upregulated in senescent human mesenchymal progenitor cells (hMPCs) whereas APOE overexpression promoted hMPC senescence. By contrast, hMPCs lacking APOE were resistant to cellular senescence with a more stable epigenome. Further analysis indicated that APOE interacted with nuclear envelope proteins including LBR and Emerin and a heterochromatin-associated protein KAP1 and interrupted heterochromatin organization via the interference of nuclear envelope homeostasis, thus leading to hMPC senescence. Mechanistically, APOE facilitated the degradation of nuclear envelope proteins through autophagy-lysosomal pathway. Lastly, we showed that knockdown of APOE had geroprotective effects in replicative or pathological hMPC senescence. Altogether, our findings uncover a new role of APOE in regulating human stem cell senescence via the disturbance of heterochromatin assembly and point to a new potential therapeutic strategy via APOE intervention in combating aging-related pathologies. |
| Sample scope |
Monoisolate |
| Release date |
2021-02-17 |
| Publication |
| PubMed ID |
Article title |
Journal name |
DOI |
Year |
|
|
Destabilizing heterochromatin by APOE mediates senescence
|
Nature Aging
|
10.1038/s43587-022-00186-z
|
2022
|
|
|
| Grants |
| Agency |
program |
Grant ID |
Grant title |
| Chinese Academy of Sciences (CAS)
|
Strategic Priority Research Program of Chinese Academy of Sciences (CAS)
|
XDA16010100
|
|
|
|
| Submitter |
Guanghui
Liu (ghliu@ioz.ac.cn)
|
| Organization |
Institute of Zoology, Chinese Academy of Sciences |
| Submission date |
2021-02-17 |
