PDF(Pubmed)
Abstract：
Introduction: The ABO blood group system has important clinical significance in the safety of blood transfusion and organ transplantation. Numerous ABO variations, especially variations in the splice sites, have been identified to be associated with some ABO subtypes. Methods: Here, we performed the c.767T>C substitution of the ABO gene in human induced pluripotent stem cells (hiPSCs) by the adenosine base editor (ABE) system and described its characteristics at the genome level in detail. Results: The hiPS cell line with c.767T>C substitution maintained a normal karyotype (46, XX), expressed pluripotency markers, and showed the capability to spontaneously differentiate into all three germ layers in vivo. The genome-wide analysis demonstrated that the c.767T>C substitution in the ABO gene did not cause any detected negative effect in hiPSCs at the genome level. The splicing transcript analysis revealed that splicing variants were observed in the hiPSCs with ABO c.767T>C substitutions. Conclusion: All these results indicated that some splicing variants occurred in hiPSCs with c.767 T>C substitution of ABO gene, which probably had a significant effect on the formation of the rare ABO*Ael05/B101 subtype.
摘要：
简介：ABO血型系统对输血和器官移植的安全性具有重要的临床意义。许多ABO变体，尤其是剪接位点的变异，已被鉴定为与一些ABO亚型相关。方法:这里,我们通过腺苷碱基编辑(ABE)系统对人诱导多能干细胞(hiPSCs)中的ABO基因进行了c.767T>C置换,并在基因组水平详细描述了其特征.结果:c.767T>C取代的hiPS细胞系保持正常核型(46,XX),表达的多能性标记，并显示出在体内自发分化为所有三个胚层的能力。全基因组分析表明,ABO基因中的c.767T>C取代在基因组水平上在hiPSC中没有引起任何检测到的负面影响。剪接转录物分析揭示在具有ABOc.767T>C取代的hiPSC中观察到剪接变体。结论：所有这些结果表明，ABO基因c.767T>C取代的hiPSCs中存在一些剪接变异，这可能对罕见ABO*Ael05/B101亚型的形成有显著影响。
