| First Author | Tan J | Year | 2024 |
| Journal | iScience | Volume | 27 |
| Issue | 3 | Pages | 109231 |
| PubMed ID | 38439966 | Mgi Jnum | J:348937 |
| Mgi Id | MGI:7611444 | Doi | 10.1016/j.isci.2024.109231 |
| Citation | Tan J, et al. (2024) ApoE maintains neuronal integrity via microRNA and H3K27me3-mediated repression. iScience 27(3):109231 |
| abstractText | ApoE regulates neurogenesis, although how it influences genetic programs remains elusive. Cortical neurons induced from isogenic control and ApoE-/- human neural stem cells (NSCs) recapitulated key transcriptomic signatures of in vivo counterparts identified from single-cell human midbrain. Surprisingly, ApoE expression in NSC and neural progenitor cells (NPCs) is not required for differentiation. Instead, ApoE prevents the over-proliferation of non-neuronal cells during extended neuronal culture when it is not expressed. Elevated miR-199a-5p level in ApoE-/- cells lowers the EZH1 protein and the repressive H3K27me3 mark, a phenotype rescued by miR-199a-5p steric inhibitor. Reduced H3K27me3 at genes linked to extracellular matrix organization and angiogenesis in ApoE-/- NPC correlates with their aberrant expression and phenotypes in neurons. Interestingly, the ApoE coding sequence, which contains many predicted miR-199a-5p binding sites, can repress miR-199a-5p without translating into protein. This suggests that ApoE maintains neurons integrity through the target-directed miRNA degradation of miR-199a-5p, imparting the H3K27me3-mediated repression of non-neuronal genes during differentiation. |
