Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA.
Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA; Computational and Systems Biology Program, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Stem Cell Reports. 2015 Nov 10;5(5):763-775. doi: 10.1016/j.stemcr.2015.09.016.
Hundreds of transcription factors (TFs) are expressed in each cell type, but cell identity can be induced through the activity of just a small number of core TFs. Systematic identification of these core TFs for a wide variety of cell types is currently lacking and would establish a foundation for understanding the transcriptional control of cell identity in development, disease, and cell-based therapy. Here, we describe a computational approach that generates an atlas of candidate core TFs for a broad spectrum of human cells. The potential impact of the atlas was demonstrated via cellular reprogramming efforts where candidate core TFs proved capable of converting human fibroblasts to retinal pigment epithelial-like cells. These results suggest that candidate core TFs from the atlas will prove a useful starting point for studying transcriptional control of cell identity and reprogramming in many human cell types.
数百种转录因子（TFs）在每种细胞类型中表达，但细胞身份可以通过少数几个核心 TFs 的活性来诱导。目前缺乏对各种细胞类型的这些核心 TFs 的系统识别，这将为理解发育、疾病和基于细胞的治疗中细胞身份的转录控制奠定基础。在这里，我们描述了一种计算方法，该方法生成了广泛的人类细胞候选核心 TF 的图谱。通过细胞重编程工作证明了图谱的潜在影响，候选核心 TF 能够将人成纤维细胞转化为视网膜色素上皮样细胞。这些结果表明，图谱中的候选核心 TF 将成为研究许多人类细胞类型中细胞身份和重编程的转录控制的有用起点。
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