真性红细胞增多症诱导性多能干细胞株的建立

Establishment of iPSC Lines from A Polycythemia Vera Patient

诱导多能性干细胞(induced pluripotent stem cell,i PSC)技术在疾病研究和临床应用上具有广阔的前景。JAK2V617F是骨髓增殖性肿瘤(myeloproliferative neoplasms,MPN),如真性红细胞增多症(polycythemia vera,PV)患者携带的一种重要突变。该研究采用非整合型质粒重编程携带JAK2V617F突变的PV患者外周血来源的单个核细胞,诱导生成携带JAK2V617F突变的i PSC。结果表明,通过这种途径形成的i PSC系可稳定传代,多能性基因表达水平与胚胎干细胞(embryonic stem cells,ES cells)类似,可稳定地在体内分化形成三胚层结构并携带不同负荷的JAK2V617F突变。这为研究JAK2V617F在PV中的发病机制、药物筛选开发及基因靶向治疗提供了一个重要的实验模型。

Abstract Induced pluripotent stem cell technology provides great advantages in basic medical research and clinical application. JAK2v617F is the predominant mutation in myeloproliferative neoplasms （MPN）, such as polycythemia vera （PV）. In this study, we used episomal vectors to generate induced pluripotent stem cell （iPSC） from a PV patient carrying the JAK2v617F mutation. The result showed that the iPSC lines we established were stable and could be passaged repeatedly. The expression levels of pluripotent genes were similar to those of ES ceils. In addition, these iPSCs carried different allele burdens ofJAK2v617F mutation and were able to form teratomas in vivo. Modeling PV with these iPSC lines will provide a new approach to study the pathogenesis as well as to screen of the compounds targeting JAK2v617F for clinical therapy.