AUTHOR=Jin Yinge , Chen Tao , Zheng Wei , Xi Jiahui , Zi Yin , Wang Jinling , Chi Yue , Chen Min , Zou Qingjian , Tang Chengcheng , Lai Liangxue , Zhou Xiaoqing 

TITLE=Generation of hiPSCs with ABO c.767T>C substitution: resulting in splicing variants

JOURNAL=Frontiers in Genetics

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2023.1141756

DOI=10.3389/fgene.2023.1141756

ISSN=1664-8021

ABSTRACT=<p><bold>Introduction:</bold> 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.</p><p><bold>Methods:</bold> Here, we performed the c.767T&gt;C substitution of the <italic>ABO</italic> 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.</p><p><bold>Results:</bold> The hiPS cell line with c.767T&gt;C substitution maintained a normal karyotype (46, XX), expressed pluripotency markers, and showed the capability to spontaneously differentiate into all three germ layers <italic>in vivo</italic>. The genome-wide analysis demonstrated that the c.767T&gt;C substitution in the <italic>ABO</italic> 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 <italic>ABO</italic> c.767T&gt;C substitutions.</p><p><bold>Conclusion:</bold> All these results indicated that some splicing variants occurred in hiPSCs with c.767 T&gt;C substitution of ABO gene, which probably had a significant effect on the formation of the rare ABO*Ael05/B101 subtype.</p>