The N-glycome regulates the endothelial-to-hematopoietic transition

Science. 2020 Dec 4;370(6521):1186-1191. doi: 10.1126/science.aaz2121. Epub 2020 Dec 3.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

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
  • beta-Galactoside alpha-2,3-Sialyltransferase


  • Glycoproteins
  • MicroRNAs
  • Polysaccharides
  • microRNA-223, zebrafish
  • Mannosyltransferases
  • Sialyltransferases
  • ADAM10 Protein
  • beta-Galactoside alpha-2,3-Sialyltransferase