Sugar code regulates blood stem cells During embryonic development, blood stem cells are derived from vascular endothelial cells that line the walls of developing arteries. The transition from endothelial cells to blood stem cells is highly regulated and restricted to a small portion of endothelial cells during a brief period of time. The mechanisms regulating this transition are also poorly understood. Kasper et al. found that microRNA-223 intrinsically restrains the vascular hematopoietic transition by regulating N-glycan biosynthesis to restrict hematopoietic stem and progenitor cell production and differentiation. Genetics or chemicals could be used to alter the sugar code and change the efficiency of blood production in embryos. Thus, genetically or pharmacologically altering N-glycan biosynthesis in endothelial cells could improve the efficiency of the production of blood stem cells, which could then be used to treat blood diseases such as leukemia. Science, this issue p. 1186 The N-glycan “sugar code” governs the hematopoietic fate of endothelial cells and regulates blood stem cell production. 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.

中文翻译：

---

N-糖组调节内皮细胞到造血细胞的转变

糖编码调节造血干细胞 在胚胎发育过程中，造血干细胞来源于发育中动脉壁上排列的血管内皮细胞。从内皮细胞到血液干细胞的转变受到高度调节，并在短时间内仅限于一小部分内皮细胞。调节这种转变的机制也知之甚少。卡斯帕等人。发现 microRNA-223 通过调节 N-聚糖生物合成来限制造血干细胞和祖细胞的产生和分化，从而本质上抑制血管造血转化。遗传学或化学物质可用于改变糖代码并改变胚胎的造血效率。因此，通过遗传学或药理学方法改变​​内皮细胞中 N-聚糖的生物合成，可以提高造血干细胞的生产效率，从而可用于治疗白血病等血液疾病。科学，这个问题 p。1186 N-聚糖“糖密码”控制内皮细胞的造血命运并调节血液干细胞的产生。最终的造血干细胞和祖细胞 (HSPC) 源自造血内皮细胞 (hemEC) 的转分化。这种内皮细胞到造血细胞转变 (EHT) 的机制知之甚少。我们表明，microRNA-223 (miR-223) 介导的内皮细胞 (EC) 中 N-聚糖生物合成的调节调节 EHT。miR-223 富含 hemEC 和寡能新生 HSPC。miR-223 通过抑制甘露糖基转移酶 alg2 和唾液酸转移酶 st3gal2（参与蛋白质 N-糖基化的两种酶）来限制淋巴-骨髓谱系的 EHT。缺乏 miR-223 的 EC 显示 N-糖蛋白（例如金属蛋白酶 Adam10）上的高甘露糖与唾液酸化糖减少。N-聚糖 Adam10 突变体或 N-糖酶表型复制 miR-223 突变体缺陷的 EC 特异性表达。因此，N-糖组是 EHT 的内在调节剂，是造血命运的关键决定因素。N-聚糖 Adam10 突变体或 N-糖酶表型复制 miR-223 突变体缺陷的 EC 特异性表达。因此，N-糖组是 EHT 的内在调节剂，是造血命运的关键决定因素。N-聚糖 Adam10 突变体或 N-糖酶表型复制 miR-223 突变体缺陷的 EC 特异性表达。因此，N-糖组是 EHT 的内在调节剂，是造血命运的关键决定因素。