The direct reprogramming of somatic cells into induced neural progenitor cells (iNPCs) has been envisioned as a promising approach to overcome ethical and clinical issues of pluripotent stem cell transplantation. We previously reported that astrocyte-derived induced pluripotent stem cells (iPSCs) have more tendencies for neuronal differentiation than fibroblast-derived iPSCs. However, the differences of neurogenic potential between astrocyte-derived iNPCs (AiNPCs) and iNPCs from non-neural origins, such as fibroblast-derived iNPCs (FiNPCs), and the underlying mechanisms remain unclear. Our results suggested that AiNPCs exhibited higher differentiation efficiency, mobility and survival capacities, compared to FiNPCs. The whole transcriptome analysis revealed higher activities of TGFβ signaling in AiNPCs, versus FiNPCs, following a similar trend between astrocytes and fibroblasts. The higher neurogenic competence, migration ability, and cell death resistance of AiNPCs could be abrogated using TGFβ signaling inhibitor LY2157299. Hence, our study demonstrates the difference between iNPCs generated from neural and non-neural cells, together with the underlying mechanisms, which, provides valuable information for donor cell selection in the reprogramming approach.

中文翻译：

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重编程的星形胶质细胞比重编程的成纤维细胞显示更高的神经源性能力，迁移能力和细胞死亡抵抗力。

已经设想了将体细胞直接重编程为诱导的神经祖细胞（iNPC），作为克服多能干细胞移植的伦理和临床问题的有前途的方法。我们以前曾报道过，与成纤维细胞衍生的iPSC相比，星形胶质细胞诱导的多能干细胞（iPSC）具有更多的神经元分化趋势。但是，星形胶质细胞衍生的iNPCs（AiNPCs）和非神经来源的iNPCs，例如成纤维细胞衍生的iNPCs（FiNPCs）之间的神经源性潜能差异，以及潜在的机制尚不清楚。我们的结果表明，与FiNPC相比，AiNPC具有更高的分化效率，流动性和生存能力。整个转录组分析显示，与FiNPC相比，AiNPC中TGFβ信号传导的活性更高，遵循星形胶质细胞和成纤维细胞之间的相似趋势。使用TGFβ信号抑制剂LY2157299可以消除AiNPCs更高的神经源性能力，迁移能力和细胞死亡抗性。因此，我们的研究证明了神经细胞和非神经细胞生成的iNPC之间的差异，以及潜在的机制，这为重编程方法中的供体细胞选择提​​供了有价值的信息。