Mura Manuela, Pisano Federica, Stefanello Manuela, Ginevrino Monia, Boni Marina, Calabrò Federica, Crotti Lia, Valente Enza Maria, Schwartz Peter J, Brink Paul A, Gnecchi Massimiliano
Coronary Care Unit and Laboratory of Experimental Cardiology for Cell and Molecular Therapy, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
Coronary Care Unit and Laboratory of Experimental Cardiology for Cell and Molecular Therapy, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.; Department of Molecular Medicine, Unit of Cardiology, Università degli studi di Pavia, Pavia, Italy.
Stem Cell Res. 2019 Apr;36:101416. doi: 10.1016/j.scr.2019.101416. Epub 2019 Mar 6.
We generated human induced pluripotent stem cells (hiPSCs) from a symptomatic Long QT Syndrome (LQTS) type 1 patient, belonging to a South African (SA) founder population segregating the heterozygous mutation c.1022C > T p.A341V on the KCNQ1 gene. The patient is also homozygous for the two minor variants rs4657139 and rs16847548 on the NOS1AP gene, associated with greater risk for cardiac arrest and sudden death in LQTS mutation carriers of the founder population. hiPSCs, obtained using four retroviruses encoding the reprogramming factors OCT4, SOX2, cMYC and KLF4, display pluripotent stem cell characteristics, and can be differentiated into spontaneously beating cardiomyocytes (hiPSC-CMs).
我们从一名患有症状性1型长QT综合征（LQTS）的患者中诱导生成了人诱导多能干细胞（hiPSC），该患者属于南非（SA）奠基者群体，其KCNQ1基因存在杂合突变c.1022C>T p.A341V。该患者在NOS1AP基因上的两个次要变体rs4657139和rs16847548也是纯合的，这两个变体与该奠基者群体中携带LQTS突变的个体发生心脏骤停和猝死的风险增加有关。使用编码重编程因子OCT4、SOX2、cMYC和KLF4的四种逆转录病毒获得的hiPSC具有多能干细胞特征，并且可以分化为自发跳动的心肌细胞（hiPSC-CM）。
