| First Author | Vargel Ö | Year | 2016 |
| Journal | Sci Rep | Volume | 6 |
| Pages | 21518 | PubMed ID | 26891705 |
| Mgi Jnum | J:259977 | Mgi Id | MGI:6102017 |
| Doi | 10.1038/srep21518 | Citation | Vargel O, et al. (2016) Activation of the TGFbeta pathway impairs endothelial to haematopoietic transition. Sci Rep 6:21518 |
| abstractText | The endothelial to haematopoietic transition (EHT) is a key developmental process where a drastic change of endothelial cell morphology leads to the formation of blood stem and progenitor cells during embryogenesis. As TGFbeta signalling triggers a similar event during embryonic development called epithelial to mesenchymal transition (EMT), we hypothesised that TGFbeta activity could play a similar role in EHT as well. We used the mouse embryonic stem cell differentiation system for in vitro recapitulation of EHT and performed gain and loss of function analyses of the TGFbeta pathway. Quantitative proteomics analysis showed that TGFbeta treatment during EHT increased the secretion of several proteins linked to the vascular lineage. Live cell imaging showed that TGFbeta blocked the formation of round blood cells. Using gene expression profiling we demonstrated that the TGFbeta signalling activation decreased haematopoietic genes expression and increased the transcription of endothelial and extracellular matrix genes as well as EMT markers. Finally we found that the expression of the transcription factor Sox17 was up-regulated upon TGFbeta signalling activation and showed that its overexpression was enough to block blood cell formation. In conclusion we showed that triggering the TGFbeta pathway does not enhance EHT as we hypothesised but instead impairs it. |
