ZFIN ID: ZDB-PUB-210112-1
The N-glycome regulates the endothelial-to-hematopoietic transition
Kasper, D.M., Hintzen, J., Wu, Y., Ghersi, J.J., Mandl, H.K., Salinas, K.E., Armero, W., He, Z., Sheng, Y., Xie, Y., Heindel, D.W., Park, E.J., Sessa, W.C., Mahal, L.K., Lebrilla, C., Hirschi, K.K., Nicoli, S.
Date: 2020
Source: Science (New York, N.Y.)   370: 1186-1191 (Journal)
Registered Authors: Ghersi, Joey, Nicoli, Stefania
Keywords: none
Microarrays: GEO:GSE135246, GEO:GSE81335, GEO:GSE81340, GEO:GSE81341
MeSH Terms:
  • ADAM10 Protein/genetics
  • ADAM10 Protein/metabolism
  • Animals
  • Animals, Genetically Modified
  • Cell Lineage
  • Cell Transdifferentiation*
  • Endothelial Cells/cytology*
  • Endothelial Cells/metabolism
  • Genes, Reporter
  • Glycomics
  • Glycoproteins/metabolism*
  • Glycosylation
  • Hematopoietic Stem Cells/cytology*
  • Hematopoietic Stem Cells/metabolism
  • Mannosyltransferases/metabolism
  • MicroRNAs/genetics
  • MicroRNAs/physiology*
  • Polysaccharides/biosynthesis*
  • Sialyltransferases/metabolism
  • Zebrafish
PubMed: 33273096 Full text @ Science
Definitive hematopoietic stem and progenitor cells (HSPCs) arise from the transdifferentiation of hemogenic endothelial cells (hemECs). The mechanisms of this endothelial-to-hematopoietic transition (EHT) are poorly understood. We show that microRNA-223 (miR-223)-mediated regulation of N-glycan biosynthesis in endothelial cells (ECs) regulates EHT. miR-223 is enriched in hemECs and in oligopotent nascent HSPCs. miR-223 restricts the EHT of lymphoid-myeloid lineages by suppressing the mannosyltransferase alg2 and sialyltransferase st3gal2, two enzymes involved in protein N-glycosylation. ECs that lack miR-223 showed a decrease of high mannose versus sialylated sugars on N-glycoproteins such as the metalloprotease Adam10. EC-specific expression of an N-glycan Adam10 mutant or of the N-glycoenzymes phenocopied miR-223 mutant defects. Thus, the N-glycome is an intrinsic regulator of EHT, serving as a key determinant of the hematopoietic fate.