Das D K, Tapias V, D'Aiuto L, Chowdari K V, Francis L, Zhi Y, Ghosh Bhattacharjee A, Surti U, Tischfield J, Sheldon M, Moore J C, Fish K, Nimgaonkar V
University of Pittsburgh School of Medicine, Dept of Psychiatry.
University of Pittsburgh, Dept. of Neurology.
Mol Neuropsychiatry. 2015 Jul;1(2):116-123. doi: 10.1159/000430916. Epub 2015 Jun 24.
Copy number variation on chromosome 15q11.2 (BP1-BP2) causes deletion of and ; it also affects brain structure and elevates risk for several neurodevelopmental disorders that are associated with dendritic spine abnormalities. In rodents, altered expression changes dendritic spine morphology, motivating analyses of human neuronal cells derived from iPSCs (iPSC-neurons).
iPSCs were generated from a mother and her offspring, both carrying the 15q11.2 (BP1-BP2) deletion, and a non-deletion control. Gene expression in the deletion region was estimated using quantitative real-time PCR assays. Neural progenitor cells (NPCs) and iPSC-neurons were characterized using immunocytochemistry.
and gene expression was lower in iPSCs, NPCs and iPSC-neurons from the mother and her offspring in relation to control cells. CYFIP1 and PSD95 protein levels were lower in iPSC-neurons derived from the CNV bearing individuals using Western blot analysis. At 10 weeks post-differentiation, iPSC-neurons appeared to show dendritic spines and qualitative analysis suggested that dendritic morphology was altered in 15q11.2 deletion subjects compared with control cells.
The 15q11.2 (BP1-BP2) deletion is associated with reduced expression of four genes in iPSC-derived neuronal cells; it may also be associated altered iPSC-neuron dendritic morphology.
15号染色体15q11.2区域（BP1 - BP2）的拷贝数变异会导致 和 的缺失；它还会影响脑结构，并增加几种与树突棘异常相关的神经发育障碍的风险。在啮齿动物中， 表达的改变会改变树突棘形态，这促使人们对源自诱导多能干细胞的人类神经元细胞（诱导多能干细胞神经元）进行分析。
从一位携带15q11.2（BP1 - BP2）缺失的母亲及其后代以及一个非缺失对照个体中获取诱导多能干细胞。使用定量实时PCR分析来估计缺失区域的基因表达。通过免疫细胞化学对神经祖细胞（NPC）和诱导多能干细胞神经元进行表征。
与对照细胞相比，来自母亲及其后代的诱导多能干细胞、神经祖细胞和诱导多能干细胞神经元中的 和 基因表达较低。使用蛋白质印迹分析发现，源自携带拷贝数变异个体的诱导多能干细胞神经元中CYFIP1和PSD95蛋白水平较低。在分化后10周时，诱导多能干细胞神经元似乎出现了树突棘，定性分析表明，与对照细胞相比，15q11.2缺失个体的树突形态发生了改变。
15q11.2（BP1 - BP2）缺失与诱导多能干细胞衍生的神经元细胞中四个基因的表达降低有关；它也可能与诱导多能干细胞神经元的树突形态改变有关。
