美国耶鲁大学医学院Stefania Nicoli、Karen K. Hirschi等研究人员合作发现，N-糖基组参与调节内皮细胞向造血细胞的转化。这一研究成果发表在2020年12月4日出版的国际学术期刊《科学》上。

研究人员表示，最终的造血干细胞和祖细胞（HSPC）来自造血内皮细胞（hemEC）的转分化。内皮细胞向造血细胞转化（EHT）的机制了解甚少。

研究人员发现，microRNA-223（miR-223）介导的内皮细胞（EC）中N-聚糖生物合成的调节可调节EHT。miR-223富含hemEC和新生寡聚HSPC。miR-223通过抑制甘露糖基转移酶alg2和唾液酸转移酶st3gal2（蛋白质N-糖基化的两个酶）来限制淋巴样髓系的EHT。与唾液酸化糖相比，缺少miR-223的EC在N-糖蛋白（例如金属蛋白酶Adam10）上的唾液酸化糖减少。EC特异性表达的N-聚糖Adam10突变体或N-糖酶表型复制的miR-223突变体缺陷。因此，N-糖基组是EHT的内在调节因子，也是造血命运的关键决定因素。

附：英文原文

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

Author: 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

Issue&Volume: 2020/12/04

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.

DOI: 10.1126/science.aaz2121

Source: https://science.sciencemag.org/content/370/6521/1186