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TRANSCRIPTION FACTORS CONTROLLING DIFFERENTIATION OF STEM CELLS

机译:控制干细胞分化的转录因子

摘要

Forced expression of a handful of transcription factors (TFs) can induce conversions between cell identities; however, the extent to which TFs can alter cell identity has not been systematically assessed. Here, we assembled a human TFome, a comprehensive expression library of 1,578 human TF clones with full coverage of the major TF families. By systematically screening the human TFome, we identified 77 individual TFs that induce loss of human-induced-pluripotent-stem-cell (hiPSC) identity, suggesting a pervasive ability for TFs to alter cell identity. Using large-scale computational cell type classification trained on thousands of tissue expression profiles, we identified cell types generated by these TFs with high efficiency and speed, without additional selections or mechanical perturbations. TF expression in adult human tissues only correlated with some of the cell lineage generated, suggesting more complexity than observation studies can explain.
机译:少数转录因子(TFs)的强制表达可以诱导细胞身份之间的转换;但是,TFs可以改变细胞身份的程度尚未得到系统的评估。在这里,我们组装了一个人TFome,这是一个1,578个人TF克隆的全面表达文库,全面覆盖了主要TF家族。通过系统地筛选人类TFome,我们鉴定了77种个体TF,它们诱导了人类诱导的多能干细胞(hiPSC)身份的丧失,表明TF具有改变细胞身份的普遍能力。使用在数千种组织表达谱上训练的大规模计算细胞类型分类,我们以高效率和速度鉴定了由这些TF产生的细胞类型,而无需进行其他选择或机械干扰。成年人类组织中的TF表达仅与所产生的某些细胞谱系有关,这表明复杂性超出了观察研究所能解释的范围。

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