PUBLICATION
The N-glycome regulates the endothelial-to-hematopoietic transition
- Authors
- 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.
- ID
- ZDB-PUB-210112-1
- Date
- 2020
- Source
- Science (New York, N.Y.) 370: 1186-1191 (Journal)
- Registered Authors
- Ghersi, Joey, Nicoli, Stefania
- Keywords
- none
- Datasets
- GEO:GSE81340, GEO:GSE135246, GEO:GSE81335, 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
Citation
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. (2020) The N-glycome regulates the endothelial-to-hematopoietic transition. Science (New York, N.Y.). 370:1186-1191.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping