Velloso C P, Simon A, Brockes J P
Department of Biochemistry and Molecular Biology, University College London, Gower Street, WC1E 6BT, London, United Kingdom.
Curr Biol. 2001 Jun 5;11(11):855-8. doi: 10.1016/s0960-9822(01)00234-2.
Cell cycle reentry and dedifferentiation of postmitotic cells are important aspects of the ability of an adult newt and other urodele amphibians to regenerate various tissues and appendages [1]. In contrast to their mammalian counterparts, newt A1 myotubes are able to reenter S phase after serum stimulation of a pathway leading to phosphorylation of the retinoblastoma protein, pRb [2]. The activity in serum is not due to mitogenic growth factors but is generated indirectly by the activation of thrombin and subsequent proteolysis [3]. In this paper we describe the formation of interspecies hybrid (heterokaryon) myotubes by the fusion of mouse C2C12 [4] and newt A1 [5, 6] myogenic cells. The C2C12 nuclei reenter the cell cycle upon serum stimulation of the hybrids, while C2C12 homokaryon myotubes remain arrested under these conditions. These findings indicate that the postmitotic arrest of the mouse nuclei is undermined by the pathway activated in the newt cytoplasm. The hybrid myotubes provide a new model for the manipulation of the postmitotic arrest in both mammalian and newt differentiated cells.
有丝分裂后细胞的细胞周期重新进入和去分化是成年蝾螈和其他有尾两栖动物再生各种组织和附肢能力的重要方面[1]。与它们的哺乳动物对应物不同，蝾螈A1肌管在血清刺激导致视网膜母细胞瘤蛋白pRb磷酸化的途径后能够重新进入S期[2]。血清中的活性不是由于促有丝分裂生长因子，而是由凝血酶的激活和随后的蛋白水解间接产生的[3]。在本文中，我们描述了通过小鼠C2C12[4]和蝾螈A1[5,6]成肌细胞融合形成种间杂交（异核体）肌管。在血清刺激杂交体时，C2C12细胞核重新进入细胞周期，而C2C12同核体肌管在这些条件下保持停滞。这些发现表明，小鼠细胞核的有丝分裂后停滞被蝾螈细胞质中激活的途径破坏。杂交肌管为操纵哺乳动物和蝾螈分化细胞中的有丝分裂后停滞提供了一个新模型。
