| First Author | Bending D | Year | 2018 |
| Journal | J Cell Biol | Volume | 217 |
| Issue | 8 | Pages | 2931-2950 |
| PubMed ID | 29941474 | Mgi Jnum | J:264610 |
| Mgi Id | MGI:6193990 | Doi | 10.1083/jcb.201711048 |
| Citation | Bending D, et al. (2018) A timer for analyzing temporally dynamic changes in transcription during differentiation in vivo. J Cell Biol 217(8):2931-2950 |
| abstractText | Understanding the mechanisms of cellular differentiation is challenging because differentiation is initiated by signaling pathways that drive temporally dynamic processes, which are difficult to analyze in vivo. We establish a new tool, Timer of cell kinetics and activity (Tocky; or toki [time in Japanese]). Tocky uses the fluorescent Timer protein, which spontaneously shifts its emission spectrum from blue to red, in combination with computer algorithms to reveal the dynamics of differentiation in vivo. Using a transcriptional target of T cell receptor (TCR) signaling, we establish Nr4a3-Tocky to follow downstream effects of TCR signaling. Nr4a3-Tocky reveals the temporal sequence of events during regulatory T cell (Treg) differentiation and shows that persistent TCR signals occur during Treg generation. Remarkably, antigen-specific T cells at the site of autoimmune inflammation also show persistent TCR signaling. In addition, by generating Foxp3-Tocky, we reveal the in vivo dynamics of demethylation of the Foxp3 gene. Thus, Tocky is a tool for cell biologists to address previously inaccessible questions by directly revealing dynamic processes in vivo. |
