| First Author | Cai W | Year | 2012 |
| Journal | Circ Res | Volume | 111 |
| Issue | 7 | Pages | 876-81 |
| PubMed ID | 22872153 | Mgi Jnum | J:212634 |
| Mgi Id | MGI:5581903 | Doi | 10.1161/CIRCRESAHA.112.270272 |
| Citation | Cai W, et al. (2012) A Nodal-to-TGFbeta cascade exerts biphasic control over cardiopoiesis. Circ Res 111(7):876-81 |
| abstractText | RATIONALE: The transforming growth factor-beta (TGFbeta) family member Nodal promotes cardiogenesis, but the mechanism is unclear despite the relevance of TGFbeta family proteins for myocardial remodeling and regeneration. OBJECTIVE: To determine the function(s) of TGFbeta family members during stem cell cardiogenesis. METHODS AND RESULTS: Murine embryonic stem cells were engineered with a constitutively active human type I Nodal receptor (caACVR1b) to mimic activation by Nodal and found to secrete a paracrine signal that promotes cardiogenesis. Transcriptome and gain- and loss-of-function studies identified the factor as TGFbeta2. Both Nodal and TGFbeta induced early cardiogenic progenitors in embryonic stem cell cultures at day 0 to 2 of differentiation. However, Nodal expression declines by day 4 due to feedback inhibition, whereas TGFbeta persists. At later stages (days 4-6), TGFbeta suppresses the formation of cardiomyocytes from multipotent Kdr(+) progenitors while promoting the differentiation of vascular smooth muscle and endothelial cells. CONCLUSIONS: Nodal induces TGFbeta, and both stimulate the formation of multipotent cardiovascular Kdr(+) progenitors. TGFbeta, however, becomes uniquely responsible for controlling subsequent lineage segregation by stimulating vascular smooth muscle and endothelial lineages and simultaneously blocking cardiomyocyte differentiation. |
