| First Author | Taylor B | Year | 2020 |
| Journal | Sci Rep | Volume | 10 |
| Issue | 1 | Pages | 14084 |
| PubMed ID | 32826933 | Mgi Jnum | J:299837 |
| Mgi Id | MGI:6490724 | Doi | 10.1038/s41598-020-71100-z |
| Citation | Taylor B, et al. (2020) TGF-beta is insufficient to induce adipocyte state loss without concurrent PPARgamma downregulation. Sci Rep 10(1):14084 |
| abstractText | Cell plasticity, the ability of differentiated cells to convert into other cell types, underlies the pathogenesis of many diseases including the transdifferentiation of adipocytes (fat cells) into myofibroblasts in the pathogenesis of dermal fibrosis. Loss of adipocyte identity is an early step in different types of adipocyte plasticity. In this study, we determine the dynamics of adipocyte state loss in response to the profibrotic cytokine TGF-beta. We use two complementary approaches, lineage tracing and live fluorescent microscopy, which both allow for robust quantitative tracking of adipocyte identity loss at the single-cell level. We find that the intracellular TGF-beta signaling in adipocytes is inhibited by the transcriptional factor PPARgamma, specifically by its ubiquitously expressed isoform PPARgamma1. However, TGF-beta can lead to adipocyte state loss when it is present simultaneously with another stimulus. Our findings establish that an integration of stimuli occurring in a specific order is pivotal for adipocyte state loss which underlies adipocyte plasticity. Our results also suggest the possibility of a more general switch-like mechanism between adipogenic and profibrotic molecular states. |
