| First Author | Ozmadenci D | Year | 2015 |
| Journal | Nat Commun | Volume | 6 |
| Pages | 7398 | PubMed ID | 26154507 |
| Mgi Jnum | J:224367 | Mgi Id | MGI:5662134 |
| Doi | 10.1038/ncomms8398 | Citation | Ozmadenci D, et al. (2015) Netrin-1 regulates somatic cell reprogramming and pluripotency maintenance. Nat Commun 6:7398 |
| abstractText | The generation of induced pluripotent stem (iPS) cells holds great promise in regenerative medicine. The use of the transcription factors Oct4, Sox2, Klf4 and c-Myc for reprogramming is extensively documented, but comparatively little is known about soluble molecules promoting reprogramming. Here we identify the secreted cue Netrin-1 and its receptor DCC, described for their respective survival/death functions in normal and oncogenic contexts, as reprogramming modulators. In various somatic cells, we found that reprogramming is accompanied by a transient transcriptional repression of Netrin-1 mediated by an Mbd3/Mta1/Chd4-containing NuRD complex. Mechanistically, Netrin-1 imbalance induces apoptosis mediated by the receptor DCC in a p53-independent manner. Correction of the Netrin-1/DCC equilibrium constrains apoptosis and improves reprogramming efficiency. Our work also sheds light on Netrin-1's function in protecting embryonic stem cells from apoptosis mediated by its receptor UNC5b, and shows that the treatment with recombinant Netrin-1 improves the generation of mouse and human iPS cells. |
