Department of Biology, Northeastern University, Boston, MA, USA.
Curr Top Microbiol Immunol. 2013;367:53-74. doi: 10.1007/82_2012_288.
Many vertebrates have the amazing ability to regenerate all or portions of appendages including limbs, tails, fins, and digits. Unfortunately, our understanding of the cellular and molecular basis of appendage regeneration is severely lacking. However, recent technological advances that facilitate the tracking of cell lineages in vivo through space and time are allowing us to address the unknowns of regeneration, such as characterizing the cells that contribute to regeneration and identifying the tissues these cells differentiate into during regeneration. Here, we describe the experiments and the surprisingly uniform results that have emerged across diverse vertebrate species when specific cell lineages have been tracked during vertebrate appendage regeneration. These investigations show that vertebrates, from zebrafish to salamanders to mammals, utilize a limited amount of cellular plasticity to regenerate missing appendages. The universal approach to appendage regeneration is not to generate pluripotent cells that then differentiate into the new organ, but instead to generate lineage-restricted cells that are propagated in a progenitor-like state. Lessons learned from these natural cases of complex tissue regeneration might inform regenerative medicine on the best approach for re-growing complex tissues.
许多脊椎动物具有令人惊叹的再生全部或部分附肢的能力,包括肢体、尾巴、鳍和手指。不幸的是,我们对附肢再生的细胞和分子基础的理解严重不足。然而,最近的技术进步使得我们能够通过空间和时间追踪细胞谱系,从而解决再生的未知问题,例如鉴定参与再生的细胞,并确定这些细胞在再生过程中分化成的组织。在这里,我们描述了当在脊椎动物附肢再生过程中追踪特定细胞谱系时,从斑马鱼到蝾螈到哺乳动物等不同脊椎动物物种中出现的实验和惊人的一致结果。这些研究表明,从斑马鱼到蝾螈再到哺乳动物等脊椎动物,利用有限的细胞可塑性来再生缺失的附肢。普遍的附肢再生方法不是产生多能细胞,然后分化成新器官,而是产生谱系受限的细胞,以祖细胞样状态增殖。从这些复杂组织的自然再生案例中获得的经验教训可能会为再生医学提供关于重新生长复杂组织的最佳方法的信息。