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从携带 RHOT1 基因(编码 Miro1)杂合突变 c.1290A>G(p.T351A)或 c.2067A>G(p.T610A)的帕金森病患者中生成两个诱导多能干细胞系和相应的同基因对照系。

Generation of two induced pluripotent stem cell lines and the corresponding isogenic controls from Parkinson's disease patients carrying the heterozygous mutations c.1290A > G (p.T351A) or c.2067A > G (p.T610A) in the RHOT1 gene encoding Miro1.

机构信息

Translational Neuroscience, Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, Luxembourg.

Translational Neuroscience, Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, Luxembourg.

出版信息

Stem Cell Res. 2023 Jun;69:103085. doi: 10.1016/j.scr.2023.103085. Epub 2023 Mar 25.

Abstract

Primary skin fibroblasts from two Parkinson's disease (PD) patients carrying distinct heterozygous mutations in the RHOT1 gene encoding Miro1, namely c.1290A > G (Miro1 p.T351A) and c.2067A > G (Miro1 p.T610A), were converted into induced pluripotent stem cells (iPSCs) by episomal reprogramming. The corresponding isogenic gene-corrected lines have been generated using CRISPR/Cas9 technology. Here, we provide a comprehensive characterization and quality assurance of both isogenic pairs, which will be used to study Miro1-related molecular mechanisms underlying neurodegeneration in iPSC-derived neuronal models (e.g., midbrain dopaminergic neurons and astrocytes).

摘要

两位帕金森病(PD)患者的皮肤成纤维细胞分别携带 RHOT1 基因中的杂合突变,即 c.1290A>G(Miro1 p.T351A)和 c.2067A>G(Miro1 p.T610A),通过外显子重编程转化为诱导多能干细胞(iPSC)。使用 CRISPR/Cas9 技术生成了相应的同源基因校正系。在这里,我们对这两对同源基因进行了全面的特征描述和质量保证,这将用于研究 iPSC 衍生的神经元模型(例如中脑多巴胺能神经元和星形胶质细胞)中与 Miro1 相关的神经退行性变的分子机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d0d1/10240566/91e9950388bc/gr1.jpg

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