Colman Alan, Dreesen Oliver
Institute of Medical Biology, Immunos, Singapore.
EMBO Rep. 2009 Jul;10(7):714-21. doi: 10.1038/embor.2009.142. Epub 2009 Jun 19.
For much of the last century, the differentiated state that characterizes the many cell types of an adult organism was thought to be stable and abrogated only in rare instances by transdifferentiation, metaplasia or cancer. This stability was thought to reside in the autoregulatory molecular circuitry that exists between the cytoplasm and the nucleus, a status quo that could be disrupted during somatic cell nuclear transfer, to reprogramme cells to a pluripotent state. Pioneering work in the 1980s showed that transdifferentiation of cell lineages could be induced by the addition of transcription factors. However, these conversions were usually confined to cell types from the same germ layer, and proof of conversion was difficult to obtain. This deficiency has now been overturned by demonstrations that exogenously added transcription factors can convert differentiated cell types into embryonic-like induced pluripotent stem cells. Here, we highlight the recent progress, and the implications of this work for our understanding of the relationship between the pluripotent and more differentiated cell states.
在上个世纪的大部分时间里，人们认为构成成年生物体多种细胞类型的分化状态是稳定的，只有在罕见的情况下，通过转分化、化生或癌症才会被消除。这种稳定性被认为存在于细胞质和细胞核之间的自动调节分子回路中，这种状态在体细胞核移植过程中可能会被打破，从而将细胞重编程为多能状态。20世纪80年代的开创性工作表明，添加转录因子可以诱导细胞谱系的转分化。然而，这些转化通常局限于来自同一胚层的细胞类型，并且很难获得转化的证据。现在，外源性添加的转录因子可以将分化的细胞类型转化为胚胎样诱导多能干细胞的证明推翻了这一缺陷。在这里，我们重点介绍了最近的进展，以及这项工作对我们理解多能细胞状态和更分化细胞状态之间关系的影响。
