Reprogramming and Differentiation in Mammals:Motifs and Mechanisms

摘要

The natural reprogramming of the mammalian egg and sperm genomes is an efficient process that takes place in less than 24hours and gives rise to a totipotent zygote. Transfer of somatic nuclei to mammalian oocytes also leads to their reprogram-ming and formation of totipotent embryos, albeit very inefficiently and requiring an activation step. Reprogramming of dif-ferentiated cells to induced pluripotent stem (iPS) cells takes place during a period of time substantially longer thanreprogramming of the egg and sperm nuclei and is significantly less efficient. The stochastic expression of endogenous pro-teins during this process would imply that controlled expression of specific proteins is crucial for reprogramming to take place.The fact that OCT4, NANOG, and SOX2 form the core components of the pluripotency circuitry would imply that control atthe transcriptional level is important for reprogramming to iPS cells. In contradistinction, the much more efficient repro-gramming of the mammalian egg and sperm genomes implies that other levels of control are necessary, such as chromatinremodeling, translational regulation, and efficient degradation of no longer needed proteins and RNAs.