Increase developmental plasticity of human keratinocytes with gene suppression
Increase developmental plasticity of human keratinocytes with gene suppression
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DOI：
10.1073/pnas.1100509108
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发表时间：
2011-08-02
影响因子：
11.1
通讯作者：
Zhong, Jiang F.
中科院分区：
文献类型：
--
作者：
Li, Shengwen Calvin;Jin, Yangsun;Zhong, Jiang F.
最近的证据表明，p53抑制提高了诱导多能干细胞（iPSC）生成的效率。即使只有两个典型的转录因子Oct4和Sox2的强制表达也会发生这种情况。在这项研究中，原代人角质形成细胞通过p53的瞬时失活成功地诱导进入可塑性阶段，而没有强制表达先前用于iPSC生成的任何转录因子。这些细胞后来再分化成神经谱系。基因抑制可塑性细胞在形态上与人ES细胞难以区分。基因抑制塑料细胞碱性磷酸酶阳性，有正常的核型，并表达p53。随着iPSC生成和癌症形成之间的相似性和重叠机制的证据越来越多，这一发现揭示了p53位于两个复杂的细胞潜能之间的十字路口的新图景：干细胞与癌细胞生成。这一发现进一步支持了p53在细胞重编程中发挥的关键作用，并提出了一种转换人类细胞谱系身份的替代方法。该报道的方法提供了定向谱系转换的可能性，其目标是产生用于神经退行性疾病的新临床应用的自体细胞群体。
Recent evidence indicates that p53 suppression increased the efficiency of induced pluripotent stem cell (iPSC) generation. This occurred even with the enforced expression of as few as two canonical transcription factors, Oct4 and Sox2. In this study, primary human keratinocytes were successfully induced into a stage of plasticity by transient inactivation of p53, without enforced expression of any of the transcription factors previously used in iPSC generation. These cells were later redifferentiated into neural lineages. The gene suppression plastic cells were morphologically indistinguishable from human ES cells. Gene suppression plastic cells were alkaline phosphatase-positive, had normal karyotypes, and expressed p53. Together with the accumulating evidence of similarities and overlapping mechanisms between iPSC generation and cancer formation, this finding sheds light on the emerging picture of p53 sitting at the crossroads between two intricate cellular potentials: stem cell vs. cancer cell generation. This finding further supports the crucial role played by p53 in cellular reprogramming and suggests an alternative method to switch the lineage identity of human cells. This reported method offers the potential for directed lineage switching with the goal of generating autologous cell populations for novel clinical applications for neurodegenerative diseases.