| First Author | Kong X | Year | 2022 |
| Journal | Nucleic Acids Res | Volume | 50 |
| Issue | 18 | Pages | 10526-10543 |
| PubMed ID | 36134711 | Mgi Jnum | J:330272 |
| Mgi Id | MGI:7367038 | Doi | 10.1093/nar/gkac780 |
| Citation | Kong X, et al. (2022) LncRNA-Smad7 mediates cross-talk between Nodal/TGF-beta and BMP signaling to regulate cell fate determination of pluripotent and multipotent cells. Nucleic Acids Res 50(18):10526-10543 |
| abstractText | Transforming growth factor beta (TGF-beta) superfamily proteins are potent regulators of cellular development and differentiation. Nodal/Activin/TGF-beta and BMP ligands are both present in the intra- and extracellular milieu during early development, and cross-talk between these two branches of developmental signaling is currently the subject of intense research focus. Here, we show that the Nodal induced lncRNA-Smad7 regulates cell fate determination via repression of BMP signaling in mouse embryonic stem cells (mESCs). Depletion of lncRNA-Smad7 dramatically impairs cardiomyocyte differentiation in mESCs. Moreover, lncRNA-Smad7 represses Bmp2 expression through binding with the Bmp2 promoter region via (CA)12-repeats that forms an R-loop. Importantly, Bmp2 knockdown rescues defects in cardiomyocyte differentiation induced by lncRNA-Smad7 knockdown. Hence, lncRNA-Smad7 antagonizes BMP signaling in mESCs, and similarly regulates cell fate determination between osteocyte and myocyte formation in C2C12 mouse myoblasts. Moreover, lncRNA-Smad7 associates with hnRNPK in mESCs and hnRNPK binds at the Bmp2 promoter, potentially contributing to Bmp2 expression repression. The antagonistic effects between Nodal/TGF-beta and BMP signaling via lncRNA-Smad7 described in this work provides a framework for understanding cell fate determination in early development. |
