Sun Junyi, Ren Lu, Canel Rivero Gabriela, Xu Lingyun, Ladabaum Uri, C Wu Joseph
Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Medicine, Division of Cardiology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Greenstone Biosciences, Palo Alto, CA 94304, USA.
Stem Cell Res. 2024 Dec;81:103527. doi: 10.1016/j.scr.2024.103527. Epub 2024 Aug 3.
Li-Fraumeni syndrome (LFS) is a rare autosomal dominant inherited genetic disorder that greatly increases the risk of developing several types of cancer, including young children and young adults. LFS is primarily caused by specific mutations in the tumor suppressor gene TP53. In this study, we successfully generated two human induced pluripotent stem cell (iPSC) lines derived from patients diagnosed with LFS, each carrying a distinct heterozygous mutation in the TP53 gene. These LFS patient-derived iPSC lines exhibited robust expression of key pluripotency markers, demonstrated the capacity to differentiate into all three germ layers (endoderm, mesoderm, and ectoderm), and maintained a normal karyotype. The establishment of these iPSC lines provides a valuable tool for modeling LFS in vitro, enabling researchers to investigate the underlying pathological mechanisms associated with the disease across various cell types and tissues.
李-弗劳梅尼综合征（LFS）是一种罕见的常染色体显性遗传疾病，会大幅增加患多种癌症的风险，包括儿童和青年。LFS主要由肿瘤抑制基因TP53的特定突变引起。在本研究中，我们成功地从被诊断患有LFS的患者中生成了两个人诱导多能干细胞（iPSC）系，每个系在TP53基因中携带一个独特的杂合突变。这些源自LFS患者的iPSC系表现出关键多能性标志物的强劲表达，展示了分化为所有三个胚层（内胚层、中胚层和外胚层）的能力，并维持了正常的核型。这些iPSC系的建立为在体外模拟LFS提供了一个有价值的工具，使研究人员能够在各种细胞类型和组织中研究与该疾病相关的潜在病理机制。
