Gene expression analysis of H9 hESC derived neuron stem cells (NSC) harboring pathogenic LRRK2 (G2019S) mutation. Homo sapiens

Genetic mutations on leucine-rich repeat kinase 2 (LRRK2) have been associated with an increased risk of Parkinson's disease. The Gly2019Ser (G2019S) mutation on LRRK2 gene is a relatively common cause of familial Parkinson's disease in Caucasian population. In this study, we generated H9 hESC harboring LRRK2 (G2019S) mutation by gene knockin. Wildtype and LRRK2 mutant hESC were differentiated into NSC using a chemically defined protocol. Overall design: LRRK2 mutant NSC were treated with or without the LRRK2 kinase specific inhibitor (LRRK2-IN-1). Global gene expression analysis was performed to assess the overall similarity of gene expression profiles among three NSC groups (wildtype; LRRK2 mutant; LRRK2 mutant with inhibitor treatment).

富亮氨酸重复激酶2（leucine-rich repeat kinase 2, LRRK2）的基因突变与帕金森病发病风险升高存在关联。LRRK2基因上的Gly2019Ser（G2019S）突变是高加索人群中家族性帕金森病较为常见的致病诱因。本研究通过基因敲入技术，构建了携带LRRK2 (G2019S)突变的H9人胚胎干细胞（human embryonic stem cell, hESC）。将野生型与LRRK2突变型人胚胎干细胞采用化学成分明确的分化方案诱导分化为神经干细胞（neural stem cell, NSC）。实验整体设计：对LRRK2突变型神经干细胞分别施加或不施加LRRK2激酶特异性抑制剂LRRK2-IN-1。通过全局基因表达分析，评估三组神经干细胞（野生型组、LRRK2突变型组、LRRK2突变型抑制剂处理组）的基因表达谱整体相似性。