The N-glycome regulates the endothelial-to-hematopoietic transition.
Dionna M Kasper, Jared Hintzen, Yinyu Wu, Joey J Ghersi, Hanna K Mandl, Kevin E Salinas, William Armero, Zhiheng He, Ying Sheng, Yixuan Xie, Daniel W Heindel, Eon Joo Park, William C Sessa, Lara K Mahal, Carlito Lebrilla, Karen K Hirschi, Stefania Nicoli
Author Information
Dionna M Kasper: Yale Cardiovascular Research Center, Department of Internal Medicine, Section of Cardiology, Yale University School of Medicine, New Haven, CT 06511, USA. ORCID
Jared Hintzen: Yale Cardiovascular Research Center, Department of Internal Medicine, Section of Cardiology, Yale University School of Medicine, New Haven, CT 06511, USA.
Yinyu Wu: Yale Cardiovascular Research Center, Department of Internal Medicine, Section of Cardiology, Yale University School of Medicine, New Haven, CT 06511, USA. ORCID
Joey J Ghersi: Yale Cardiovascular Research Center, Department of Internal Medicine, Section of Cardiology, Yale University School of Medicine, New Haven, CT 06511, USA.
Hanna K Mandl: Yale Cardiovascular Research Center, Department of Internal Medicine, Section of Cardiology, Yale University School of Medicine, New Haven, CT 06511, USA.
Kevin E Salinas: Yale Cardiovascular Research Center, Department of Internal Medicine, Section of Cardiology, Yale University School of Medicine, New Haven, CT 06511, USA. ORCID
William Armero: Yale Cardiovascular Research Center, Department of Internal Medicine, Section of Cardiology, Yale University School of Medicine, New Haven, CT 06511, USA. ORCID
Zhiheng He: Yale Cardiovascular Research Center, Department of Internal Medicine, Section of Cardiology, Yale University School of Medicine, New Haven, CT 06511, USA.
Ying Sheng: Department of Chemistry, University of California, Davis, CA 95616, USA. ORCID
Yixuan Xie: Department of Chemistry, University of California, Davis, CA 95616, USA. ORCID
Daniel W Heindel: Biomedical Chemistry Institute, Department of Chemistry, New York University, New York, NY 10003, USA. ORCID
Eon Joo Park: Vascular Biology and Therapeutics Program, Yale University School of Medicine, New Haven, CT 06520, USA.
William C Sessa: Vascular Biology and Therapeutics Program, Yale University School of Medicine, New Haven, CT 06520, USA. ORCID
Lara K Mahal: Biomedical Chemistry Institute, Department of Chemistry, New York University, New York, NY 10003, USA. ORCID
Carlito Lebrilla: Department of Chemistry, University of California, Davis, CA 95616, USA. ORCID
Karen K Hirschi: Yale Cardiovascular Research Center, Department of Internal Medicine, Section of Cardiology, Yale University School of Medicine, New Haven, CT 06511, USA. stefania.nicoli@yale.edu kkh4yy@virginia.edu. ORCID
Stefania Nicoli: Yale Cardiovascular Research Center, Department of Internal Medicine, Section of Cardiology, Yale University School of Medicine, New Haven, CT 06511, USA. stefania.nicoli@yale.edu kkh4yy@virginia.edu. ORCID
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 and sialyltransferase , 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.
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