The N-Glycome regulates the endothelial-to-hematopoietic transition
Glycome
Glycomics
Hematopoietic stem cell
DOI:
10.1101/602912
Publication Date:
2019-04-10T00:06:40Z
AUTHORS (17)
ABSTRACT
Abstract Hematopoietic stem and progenitor cells (HSPCs) that establish maintain the blood system in adult vertebrates arise from transdifferentiation of hemogenic endothelial (hemECs) during embryogenesis. This endothelial-to-hematopoietic transition (EHT) is tightly regulated, but mechanisms are poorly understood. Here, we show microRNA (miR)-223-mediated regulation N-glycan biosynthesis (ECs) regulates EHT. Single cell RNA-sequencing revealed miR-223 enriched hemECs oligopotent nascent HSPCs. restricts EHT lymphoid/myeloid lineages by suppressing expression mannosyltransferase alg2 sialyltransferase st3gal2 , two enzymes involved N-linked protein glycosylation. High-throughput glycomics ECs lacking showed a decrease high mannose versus sialylated complex/hybrid sugars on N-glycoproteins such as metalloprotease Adam10. Endothelial-specific an Adam10 mutant or N-glycoenzymes phenocopied aberrant HSPC production mutants. Thus, N-glycome plays previously unappreciated role intrinsic regulator EHT, with specific sialic acid modifications serving key determinants their hematopoietic fate. One Sentence Summary The “sugar code” governs fate vivo.
SUPPLEMENTAL MATERIAL
Coming soon ....
REFERENCES (27)
CITATIONS (1)
EXTERNAL LINKS
PlumX Metrics
RECOMMENDATIONS
FAIR ASSESSMENT
Coming soon ....
JUPYTER LAB
Coming soon ....