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Homeodomain protein code specifying progenitor cell identify and neuronal fate in the ventral neural tube

机译:同源神经元蛋白质代码,指定腹侧神经管中的祖细胞识别和神经元命运

摘要

Provided are genetically engineered cells comprising a neural stem cell and retroviral expression system in the neural stem cell, which is capable of expressing homeodomain transcription factor Nkx6.1 protein but does not express homeodomain transcription factor Irx3 protein or homeodomain transcription factor Nkx2.2 protein; which is capable of expressing homeodomain transcription factor Nkx6.1 protein and homeodomain transcription factor Irx3 protein; and which is capable of expressing homeodomain transcription factor Nkx2.2 protein or homeodomain transcription factor Nkx2.9 protein. Also provided are methods of generating such genetically engineered motor neurons, V2 neurons, and V3 neurons. Also provided are methods of treating subjects having a motor neuron injury or a motor neuron disease comprising implanting in injured/diseased neural tissue of the subject any of the provided genetically engineered cells, administering to such neural tissue retroviral expression systems which are capable of expressing the appropriate homeodomain protein(s), or transfecting neural stem cells with a retroviral vector, which is capable of expressing the required homeodomain transcription factor protein(s). Provided is a method of determining whether a chemical compound affects the generation of a motor neuron from a neural stem cell.
机译:提供了基因工程细胞,其包括神经干细胞和神经干细胞中的逆转录病毒表达系统,其能够表达同源结构域转录因子Nkx6.1蛋白但不表达同源结构域转录因子Irx3蛋白或同源结构域转录因子Nkx2.2蛋白;能够表达同源域转录因子Nkx6.1蛋白和同源域转录因子Irx3蛋白;并且能够表达同源域转录因子Nkx2.2蛋白或同源域转录因子Nkx2.9蛋白。还提供了产生这种基因工程的运动神经元,V2神经元和V3神经元的方法。还提供了治疗患有运动神经元损伤或运动神经元疾病的受试者的方法,该方法包括将任何提供的基因工程细胞植入受试者的受伤/患病的神经组织中,并向这种神经组织逆转录病毒表达系统施用,所述逆转录病毒表达系统能够表达合适的同源域蛋白,或用逆转录病毒载体转染神经干细胞,该载体能够表达所需的同源域转录因子蛋白。提供一种确定化合物是否影响神经干细胞产生运动神经元的方法。

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