Gene array analysis of neural crest cells identifies transcription factors necessary for direct conversion of embryonic fibroblasts into neural crest cells.
Gene array analysis of neural crest cells identifies transcription factors necessary for direct conversion of embryonic fibroblasts into neural crest cells.
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DOI：
10.1242/bio.015735
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发表时间：
2016-02-12
期刊：
影响因子：
2.4
通讯作者：
Kunisada T
中科院分区：
文献类型：
--
作者：
Motohashi T;Watanabe N;Nishioka M;Nakatake Y;Yulan P;Mochizuki H;Kawamura Y;Ko MS;Goshima N;Kunisada T
神经嵴细胞（NC 细胞）是从神经褶皱边缘出现并在整个发育胚胎中迁移的多能细胞。尽管NC细胞生成的基因调控网络已被详细阐明，但尚未揭示该网络中的哪些因素对于指导NC身份至关重要。在这项研究中，我们分析了从 Sox10-IRES-Venus 小鼠中分离出的纯 NC 亚群的基因表达谱，并研究了这些基因是否在 Sox10-IRES-Venus 小鼠胚胎成纤维细胞 (MEF) 直接转化为 NC 细胞的过程中发挥了关键作用。 9.5 天胚胎中 NC 细胞和神经管细胞的比较分子谱揭示了在发育中的躯干 NC 细胞中选择性表达的基因，包括转录因子。在测试的 25 个 NC 细胞特异性转录因子基因中，SOX10 和 SOX9 能够将 MEF 转化为 SOX10 阳性 (SOX10+) 细胞。 SOX10+细胞随后被证明可以分化为神经元、神经胶质细胞、平滑肌细胞、脂肪细胞和成骨细胞。这些SOX10+细胞还表现出有限的自我更新能力，表明SOX10和SOX9直接将MEF转化为NC细胞。相反，其余的转录因子，包括众所周知的 NC 细胞特异性因子，无法将 MEF 转化为 SOX10+ NC 细胞。这些结果表明 SOX10 和 SOX9 是 MEF 直接转化为 NC 细胞所需的关键因素。摘要：在本研究中，我们鉴定了发育中的神经嵴细胞中特异表达的转录因子，并表明 SOX10 和 SOX9 直接将成纤维细胞转化为神经嵴细胞。
Neural crest cells (NC cells) are multipotent cells that emerge from the edge of the neural folds and migrate throughout the developing embryo. Although the gene regulatory network for generation of NC cells has been elucidated in detail, it has not been revealed which of the factors in the network are pivotal to directing NC identity. In this study we analyzed the gene expression profile of a pure NC subpopulation isolated from Sox10-IRES-Venus mice and investigated whether these genes played a key role in the direct conversion of Sox10-IRES-Venus mouse embryonic fibroblasts (MEFs) into NC cells. The comparative molecular profiles of NC cells and neural tube cells in 9.5-day embryos revealed genes including transcription factors selectively expressed in developing trunk NC cells. Among 25 NC cell-specific transcription factor genes tested, SOX10 and SOX9 were capable of converting MEFs into SOX10-positive (SOX10+) cells. The SOX10+ cells were then shown to differentiate into neurons, glial cells, smooth muscle cells, adipocytes and osteoblasts. These SOX10+ cells also showed limited self-renewal ability, suggesting that SOX10 and SOX9 directly converted MEFs into NC cells. Conversely, the remaining transcription factors, including well-known NC cell specifiers, were unable to convert MEFs into SOX10+ NC cells. These results suggest that SOX10 and SOX9 are the key factors necessary for the direct conversion of MEFs into NC cells. Summary: In this study, we identified the transcription factors specifically expressed in developing neural crest cells, and showed that SOX10 and SOX9 directly converted fibroblasts into neural crest cells.