Neural crest cells (NCCs) are highly migratory multipotent cells that play critical roles in embryogenesis. The generation of NCCs is controlled by various transcription factors (TFs) that are regulated by each other and combine to form a regulatory network. We previously reported that the conversion of mouse fibroblasts into NCCs was achieved by the overexpression of only one TF, Sox10; therefore, Sox10 may be a powerful inducer of the conversion of NCCs. We herein investigated whether Sox10 functions in the direct conversion of other somatic cells into NCCs. Sox10 directly converted bone marrow-derived mesenchymal cells, but not keratinocytes, into P75+ NCCs. However, by the co-expression of four TFs (Snail1, Snail2, Twist1, and Tcfap2a) that are involved in NCC generation, but unable convert cells into NCCs, Sox10 converted keratinocytes into P75+ NCCs. P75+ NCCs mainly differentiated into glial cells, and to a lesser extent into neuronal cells. On the other hand, when Sox10 was expressed after the four TF expression, which mimicked the expression order in in vivo NCC generation, it converted keratinocytes into multipotent NCCs. These results demonstrate that Sox10 functions as an inducer of direct conversion into NCCs in cooperation with the TFs involved in NCC generation. The sequence of expression of the inducer and cooperative factors is important for the conversion of somatic cells into bona fide target cells.

中文翻译：

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Sox10 作为角质形成细胞直接转化为神经嵴细胞的诱导剂

神经嵴细胞 (NCCs) 是高度迁移的多能细胞，在胚胎发生中起关键作用。NCCs的产生受各种转录因子（TFs）控制，这些转录因子相互调控并结合形成调控网络。我们之前报道过，小鼠成纤维细胞向 NCC 的转化是通过仅一种 TF，Sox10 的过表达实现的；因此，Sox10 可能是 NCC 转化的强大诱导剂。我们在此研究了 Sox10 是否在其他体细胞直接转化为 NCC 中起作用。Sox10 直接将骨髓来源的间充质细胞而非角质形成细胞转化为 P75+ NCC。然而，通过参与 NCC 生成但无法将细胞转化为 NCC 的四种 TF（Snail1、Snail2、Twist1 和 Tcfap2a）的共表达，Sox10 将角质形成细胞转化为 P75+ NCC。P75+ NCCs 主要分化为神经胶质细胞，并在较小程度上分化为神经元细胞。另一方面，当 Sox10 在四个 TF 表达后表达时，模拟了体内 NCC 生成中的表达顺序，它将角质形成细胞转化为多能 NCC。这些结果表明，Sox10 与参与 NCC 生成的 TF 合作，充当直接转化为 NCC 的诱导剂。诱导因子和协同因子的表达顺序对于体细胞转化为重要的 它将角质形成细胞转化为多能 NCC。这些结果表明，Sox10 与参与 NCC 生成的 TF 合作，充当直接转化为 NCC 的诱导剂。诱导因子和协同因子的表达顺序对于体细胞转化为重要的 它将角质形成细胞转化为多能 NCC。这些结果表明，Sox10 与参与 NCC 生成的 TF 合作，充当直接转化为 NCC 的诱导剂。诱导因子和协同因子的表达顺序对于体细胞转化为重要的真正的靶细胞。