| First Author | Chen S | Year | 2024 |
| Journal | EMBO Rep | Volume | 25 |
| Issue | 10 | Pages | 4433-4464 |
| PubMed ID | 39256596 | Mgi Jnum | J:355696 |
| Mgi Id | MGI:7750213 | Doi | 10.1038/s44319-024-00243-1 |
| Citation | Chen S, et al. (2024) Terminal alpha1,2-fucosylation of glycosphingolipids by FUT1 is a key regulator in early cell-fate decisions. EMBO Rep 25(10):4433-4464 |
| abstractText | The embryonic cell surface is rich in glycosphingolipids (GSLs), which change during differentiation. The reasons for GSL subgroup variation during early embryogenesis remain elusive. By combining genomic approaches, flow cytometry, confocal imaging, and transcriptomic data analysis, we discovered that alpha1,2-fucosylated GSLs control the differentiation of human pluripotent cells (hPCs) into germ layer tissues. Overexpression of alpha1,2-fucosylated GSLs disrupts hPC differentiation into mesodermal lineage and reduces differentiation into cardiomyocytes. Conversely, reducing alpha1,2-fucosylated groups promotes hPC differentiation and mesoderm commitment in response to external signals. We find that bone morphogenetic protein 4 (BMP4), a mesodermal gene inducer, suppresses alpha1,2-fucosylated GSL expression. Overexpression of alpha1,2-fucosylated GSLs impairs SMAD activation despite BMP4 presence, suggesting alpha-fucosyl end groups as BMP pathway regulators. Additionally, the absence of alpha1,2-fucosylated GSLs in early/late mesoderm and primitive streak stages in mouse embryos aligns with the hPC results. Thus, alpha1,2-fucosylated GSLs may regulate early cell-fate decisions and embryo development by modulating cell signaling. |
