| First Author | Bernardes de Jesus B | Year | 2018 |
| Journal | Nat Commun | Volume | 9 |
| Issue | 1 | Pages | 94 |
| PubMed ID | 29311544 | Mgi Jnum | J:258299 |
| Mgi Id | MGI:6114852 | Doi | 10.1038/s41467-017-01921-6 |
| Citation | Bernardes de Jesus B, et al. (2018) Silencing of the lncRNA Zeb2-NAT facilitates reprogramming of aged fibroblasts and safeguards stem cell pluripotency. Nat Commun 9(1):94 |
| abstractText | Aging imposes a barrier to somatic cell reprogramming through poorly understood mechanisms. Here, we report that fibroblasts from old mice express higher levels of Zeb2, a transcription factor that activates epithelial-to-mesenchymal transition. Synthesis of Zeb2 protein is controlled by a natural antisense transcript named Zeb2-NAT. We show that transfection of adult fibroblasts with specific LNA Gapmers induces a robust downregulation of Zeb2-NAT transcripts and Zeb2 protein and enhances the reprogramming of old fibroblasts into pluripotent cells. We further demonstrate that Zeb2-NAT expression is precociously activated by differentiation stimuli in embryonic stem (ES) cells. By knocking down Zeb2-NAT, we were able to maintain ES cells challenged with commitment signals in the ground state of pluripotency. In conclusion, our study identifies a long noncoding RNA that is overlapping and antisense to the Zeb2 locus as a target for rejuvenation strategies. |
