Reprogrammed astrocytes display higher neurogenic competence, migration ability and cell death resistance than reprogrammed fibroblasts.
Reprogrammed astrocytes display higher neurogenic competence, migration ability and cell death resistance than reprogrammed fibroblasts.
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与重编程的成纤维细胞相比，重编程的星形胶质细胞表现出更高的神经发生能力、迁移能力和细胞死亡抵抗力。
DOI：
10.1186/s40035-020-0184-6
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发表时间：
2020
影响因子：
12.6
通讯作者：
Jialin C. Zheng
中科院分区：
文献类型：
--
作者：
Xiaohuan Xia;Chunhong Li;Yi Wang;Xiaobei Deng;Yizhao Ma;Lu Ding;Jialin C. Zheng
体细胞直接重编程为诱导神经前体细胞被认为是克服多能干细胞移植的伦理和临床问题的一种有前途的方法。我们之前曾报道，星形胶质细胞来源的多能干细胞(IPSCs)比成纤维细胞来源的IPSCs具有更多的神经分化倾向。然而，星形胶质细胞来源的诱导性神经前体细胞与非神经来源的诱导性神经前体细胞(如成纤维细胞来源的诱导性神经前体细胞)之间的神经分化潜能的差异及其可能的机制尚不清楚。我们的结果表明，与FiNPC相比，AiNPC具有更高的分化效率、迁移能力和存活能力。整个转录组分析显示，转化生长因子β信号在AiNPC中的活性高于FiNPC，与星形胶质细胞和成纤维细胞的趋势相似。转化生长因子β信号转导抑制剂LY2157299可抑制AiNPC较高的神经原性、迁移能力和抗细胞死亡能力。因此，我们的研究证明了神经和非神经细胞产生的iNPC的差异及其潜在的机制，这为重编程方法中的供体细胞选择提供了有价值的信息。
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.