☆ 4.8 Article

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

SCIENCE (2020)

Journal

SCIENCE

Volume 370, Issue 6521, Pages 1186-+

Publisher

AMER ASSOC ADVANCEMENT SCIENCE

DOI: 10.1126/science.aaz2121

Keywords

Funding

NIH [F32HL132475, U54DK106857, 1K99HL141687, R01HL130246, R56DK118728, R01HL146056, R01HL128064, R01DK118728, R01GM049077]
AHA [19PRE34380749, 19TPA34890046]

Ask authors/readers for more resources

Protocol

Community support

Reagent

Community support

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.

Authors

I am an author on this paper

Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.8

Not enough ratings

Secondary Ratings

Novelty

Significance

Scientific rigor

Rate this paper

Comments

Wai Lo: In embryonic development, some endothelial cells lining blood vessels transform into blood-producing stem cells. Karen Hirschi and Stefania Nicoli at Yale University, and their team, studied this process in zebrafish. They found that specific sugars on the endothelial cells' surface trigger a geneti...

View all →

Nupr1 Negatively Regulates Endothelial to Hematopoietic Transition in the Aorta-Gonad-Mesonephros Region

Haizhen Wang, Di Liu, Haifeng Chen, Yuqing Jiao, Haixin Zhao, Zongcheng Li, Siyuan Hou, Yanli Ni, Rong Zhang, Jinyong Wang, Jie Zhou, Bing Liu, Yu Lan

Summary: During the development of mid-gestational mouse embryos, specialized endothelial cells called hemogenic endothelial cells (HECs) differentiate into hematopoietic stem and progenitor cells (HSPCs) through a process called endothelial-to-hematopoietic transition (EHT). This study reveals that the gene Nupr1, previously identified as a signature gene of HECs, negatively regulates the EHT process. Deletion of Nupr1 in endothelial cells leads to increased HSPC generation in the aorta-gonad-mesonephros region. The study also finds that the proinflammatory cytokine TNF-alpha is upregulated in Nupr1-deficient HECs, and neutralizing TNF-alpha partially reduces excessive HSPC generation. These findings suggest that Nupr1 could be a potential target for future research on hematopoietic stem cell regeneration.

ADVANCED SCIENCE (2023)