Terminal α1,2-fucosylation of glycosphingolipids by FUT1 is a key regulator in early cell-fate decisions.
Saray ChenDana Hayoun-NeemanMichal NagarSapir PinyanLimor HadadLiat YaacobovLilach AlonLiraz Efrat ShacharTair SwissaOlga KryukovOrly Gershoni-YahalomBenyamin RosentalSmadar CohenRachel G LichtensteinPublished in: EMBO reports (2024)
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 α1,2-fucosylated GSLs control the differentiation of human pluripotent cells (hPCs) into germ layer tissues. Overexpression of α1,2-fucosylated GSLs disrupts hPC differentiation into mesodermal lineage and reduces differentiation into cardiomyocytes. Conversely, reducing α1,2-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 α1,2-fucosylated GSL expression. Overexpression of α1,2-fucosylated GSLs impairs SMAD activation despite BMP4 presence, suggesting α-fucosyl end groups as BMP pathway regulators. Additionally, the absence of α1,2-fucosylated GSLs in early/late mesoderm and primitive streak stages in mouse embryos aligns with the hPC results. Thus, α1,2-fucosylated GSLs may regulate early cell-fate decisions and embryo development by modulating cell signaling.
Keyphrases
- cell fate
- data analysis
- flow cytometry
- mesenchymal stem cells
- single cell
- transcription factor
- cell surface
- high resolution
- signaling pathway
- endothelial cells
- gene expression
- randomized controlled trial
- clinical trial
- epithelial mesenchymal transition
- copy number
- cell therapy
- cell death
- transforming growth factor
- dna methylation
- rna seq
- cell cycle arrest
- mass spectrometry
- bone regeneration
- bone marrow