| Literature DB >> 33273096 |
Dionna M Kasper1,2,3, Jared Hintzen1,2,3, Yinyu Wu1,2,3, Joey J Ghersi1,2,3, Hanna K Mandl1,2,3, Kevin E Salinas1,2,3, William Armero1,2,3, Zhiheng He1,2,3, Ying Sheng4, Yixuan Xie4, Daniel W Heindel5, Eon Joo Park3,6, William C Sessa3,6, Lara K Mahal5,7, Carlito Lebrilla4, Karen K Hirschi8,2,3,9, Stefania Nicoli8,2,3,6.
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.Entities:
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Year: 2020 PMID： 33273096 PMCID： PMC8312266 DOI： 10.1126/science.aaz2121
Source DB: PubMed Journal: Science ISSN： 0036-8075 Impact factor: 47.728