公开(公告)号：US20170016886A1

公开(公告)日：2017-01-19

申请号：US15221217

申请日：2016-07-27

Applicant: KOREA ADVANCED INSTITUTE OF SCIENCE AND TECHNOLOGY

Inventor： Yong-Mahn HAN ,  Young Hee Ju

IPC: G01N33/50

CPC classification number: G01N33/5073 ,  C12N5/0618 ,  C12N5/0696 ,  C12N2506/1307 ,  C12N2506/45 ,  G01N33/5023 ,  G01N33/5026 ,  G01N33/5058 ,  G01N2800/385

Abstract: The present invention relates to an induced pluripotent stem cell (iPSC) model of Noonan syndrome, a preparation method thereof, and uses to study of the pathogenesis of Noonan syndrome and a therapeutic agent screening method. Particularly, induced pluripotent stem cells from dermal fibroblasts of a Noonan syndrome-patient (NS-iPSCs) were generated, and differentiated into embryoid bodies (EBs), neural rosettes and neural cells. These iPSCs exhibited the normal morphology while showed reduced differentiation potency compare to control cell lines. NS-iPSCs were developed into embryoid bodies and neural rosettes by naturally and chemically directed differentiation. Interestingly, embryoid bodies and neural rosettes induced via chemically directed differentiation exhibited normal morphology and expressed ectoderm, neural rosettes and neural marker genes similar to normal cells. Thus, the cellular model can be useful in analytical research to understand pathogenesis of Noonan syndrome and establish screening method of the therapeutic agent.

Abstract translation: 本发明涉及Noonan综合征的诱导多能干细胞（iPSC）模型及其制备方法，用于研究Noonan综合征的发病机理和治疗剂筛选方法。 特别是，产生了一个Noonan综合征患者（NS-iPSCs）的真皮成纤维细胞诱导的多能干细胞，并分化为胚状体（EB），神经花环和神经细胞。 与对照细胞系相比，这些iPSC显示出正常的形态，同时显示出降低的分化效力。 NS-iPSCs通过自然和化学指导的分化发育成胚状体和神经花环。 有趣的是，通过化学指导的分化诱导的胚状体和神经花环呈现与正常细胞相似的正常形态和表达的外胚层，神经花环和神经标记基因。 因此，细胞模型可用于分析研究，以了解Noonan综合征的发病机制，并建立治疗药物的筛选方法。