Department of MCD Biology and Neuroscience Research Institute, University of California Santa Barbara, CA, USA.
FEBS Lett. 2018 Mar;592(6):838-851. doi: 10.1002/1873-3468.12977. Epub 2018 Feb 1.
In animal embryos, cells transition from a multipotential state, with the capacity to adopt multiple fates, into an irreversible, committed state of differentiation. This multipotency-to-commitment transition (MCT) is evident from experiments in which cell fate is reprogrammed by transcription factors for cell type-specific differentiation, as has been observed extensively in Caenorhabditis elegans. Although factors that direct differentiation into each of the three germ layer types cannot generally reprogram cells after the MCT in this animal, transcription factors for endoderm development are able to do so in multiple differentiated cell types. In one case, these factors can redirect the development of an entire organ in the process of "transorganogenesis". Natural transdifferentiation also occurs in a small number of differentiated cells during normal C. elegans development. We review these reprogramming and transdifferentiation events, highlighting the cellular and developmental contexts in which they occur, and discuss common themes underlying direct cell lineage reprogramming. Although certain aspects may be unique to the model system, growing evidence suggests that some mechanisms are evolutionarily conserved and may shed light on cellular plasticity and disease in humans.
在动物胚胎中，细胞从具有多种分化潜能的状态转变为不可逆的、特化的分化状态。这种多能性到特化的转变（MCT）可以通过转录因子对细胞类型特异性分化的实验来证明，这在秀丽隐杆线虫中得到了广泛的观察。尽管在这种动物中，指导向三个胚层类型中的每一个分化的因子通常不能在 MCT 之后重新编程细胞，但内胚层发育的转录因子能够在多种分化细胞类型中做到这一点。在一种情况下，这些因子可以在“器官间发生”的过程中重新引导整个器官的发育。在正常的秀丽隐杆线虫发育过程中，也有少数分化细胞发生自然转分化。我们回顾了这些重编程和转分化事件，强调了它们发生的细胞和发育背景，并讨论了直接细胞谱系重编程的共同主题。尽管某些方面可能是模型系统所特有的，但越来越多的证据表明，一些机制在进化上是保守的，可能为人类的细胞可塑性和疾病提供启示。
