Centre for Genetics and Genomics and Children's Brain Tumour Research Centre, University of Nottingham, Queen's Medical Centre, Nottingham NG7 2UH, United Kingdom.
Proc Natl Acad Sci U S A. 2012 Mar 13;109(11):4209-14. doi: 10.1073/pnas.1118885109. Epub 2012 Feb 27.
In most sexually reproducing animals, replication and maintenance of telomeres occurs in the germ line and during early development in embryogenesis through the use of telomerase. Somatic cells generally do not maintain telomere sequences, and these cells become senescent in adults as telomeres shorten to a critical length. Some animals reproduce clonally and must therefore require adult somatic mechanisms for maintaining their chromosome ends. Here we study the telomere biology of planarian flatworms with apparently limitless regenerative capacity fueled by a population of highly proliferative adult stem cells. We show that somatic telomere maintenance is different in asexual and sexual animals. Asexual animals maintain telomere length somatically during reproduction by fission or when regeneration is induced by amputation, whereas sexual animals only achieve telomere elongation through sexual reproduction. We demonstrate that this difference is reflected in the expression and alternate splicing of the protein subunit of the telomerase enzyme. Asexual adult planarian stem cells appear to maintain telomere length over evolutionary timescales without passage through a germ-line stage. The adaptations we observe demonstrate indefinite somatic telomerase activity in proliferating stem cells during regeneration or reproduction by fission, and establish planarians as a pertinent model for studying telomere structure, function, and maintenance.
在大多数有性繁殖的动物中,端粒的复制和维持发生在生殖细胞中,并在胚胎发生的早期发育中通过端粒酶来完成。体细胞通常不维持端粒序列,这些细胞在成年时会因为端粒缩短到临界长度而衰老。一些动物进行无性繁殖,因此必须依赖成年体细胞机制来维持染色体末端。在这里,我们研究了具有明显无限再生能力的扁形动物(例如涡虫)的端粒生物学,这种再生能力是由一群高度增殖的成年干细胞提供的。我们发现,无性繁殖和有性繁殖的动物的体细胞端粒维持方式不同。无性繁殖的动物在分裂生殖或通过截肢诱导再生时,通过分裂生殖在体细胞中维持端粒长度,而有性繁殖的动物仅通过有性繁殖才能实现端粒延长。我们证明,这种差异反映在端粒酶蛋白亚基的表达和可变剪接中。无性繁殖的成年涡虫干细胞似乎在进化时间尺度内维持端粒长度,而无需经过生殖细胞阶段。我们观察到的这些适应表明,在通过分裂生殖进行再生或繁殖时,增殖干细胞中存在无限的端粒酶活性,并确立了扁形动物作为研究端粒结构、功能和维持的相关模型。