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 Aug;39:101510. doi: 10.1016/j.scr.2019.101510. Epub 2019 Jul 24.
We generated PSMi001-A and PSMi008-A hiPSC lines from two individuals belonging to a South African (SA) founder population in which the malignant KCNQ1-A341V mutation cosegregates with the Long QT Syndrome (LQTS) phenotype. PSMi001-A was derived from an asymptomatic KCNQ1-A341V mutation carrier, whereas PSMi008-A was derived from a healthy non-mutation carrier, heterozygous for the minor variant rs16847548 on the NOS1AP gene, associated with QT prolongation in the general population, and with a greater risk for cardiac arrest in the affected members of the SA founder population. The hiPSCs, generated using the Yamanaka's retroviruses, display pluripotent stem cell features and trilineage differentiation potential.
我们从属于南非（SA）奠基人群体的两名个体中生成了PSMi001-A和PSMi008-A人诱导多能干细胞系，在该群体中，恶性KCNQ1-A341V突变与长QT综合征（LQTS）表型共分离。PSMi001-A来自一名无症状的KCNQ1-A341V突变携带者，而PSMi008-A来自一名健康的非突变携带者，其在NOS1AP基因上为次要变异rs16847548的杂合子，该变异在普通人群中与QT延长相关，并且在SA奠基人群体的患病成员中发生心脏骤停的风险更高。使用山中逆转录病毒生成的人诱导多能干细胞具有多能干细胞特征和三系分化潜能。
