RNA-Seq, raw count

To address our objectives of studying the consequences of acetylation alteration during neuronal differentiation, the first phase of this work will be the generation of iPSCs-derived neurons from fibroblasts of RSTS patients carrying the same CREBBP mutation. The second phase will concern the characterization of acetylation profiles in cells from patients in comparison with control cases. This second step will allow us to characterize the proteins whose acetylation profile is specifically altered in RSTS and the associated biological pathways. In the 3rd phase of the work, we will study the functional impact of these epigenetic alterations on neuronal differentiation by analysing the transcriptome by RNA-Seq.

为达成我们探究神经元分化过程中乙酰化修饰改变所产生的效应这一研究目标，本工作的第一阶段将从携带相同CREB结合蛋白（CREB-binding protein, CREBBP）突变的鲁宾斯坦-泰比综合征（Rubinstein-Taybi Syndrome, RSTS）患者的成纤维细胞中，制备诱导多能干细胞（induced pluripotent stem cells, iPSCs）分化而来的神经元。本研究的第二阶段将聚焦于对比分析患者来源细胞与对照样本的乙酰化修饰谱特征。通过该步骤，我们能够鉴定在RSTS中乙酰化修饰谱发生特异性改变的蛋白质及其所关联的生物学通路。在本研究的第三阶段，我们将通过RNA测序（RNA-Seq）分析转录组，探究这些表观遗传修饰改变对神经元分化过程的功能性影响。