Institute of Biotechnology, National Taiwan University, Taipei 106, Taiwan.
Center for Advanced Models for Translational Sciences and Therapeutics, University of Michigan Medical Center, Ann Arbor, MI 48109, USA.
Int J Mol Sci. 2019 Mar 12;20(5):1236. doi: 10.3390/ijms20051236.
Mammalian telomere lengths are primarily regulated by telomerase, consisting of a reverse transcriptase protein (TERT) and an RNA subunit (). We previously reported the generation of mouse and embryonic stem cells (ntESCs) by somatic cell nuclear transfer. In the present work, we investigated the germ layer development competence of , and wild-type () ntESCs. The telomere lengths are longest in wild-type but shortest in ntESCs, and correlate reversely with the population doubling time. Interestingly, while in vitro embryoid body (EB) differentiation assay reveals EB size difference among ntESCs of different genotypes, the more stringent in vivo teratoma assay demonstrates that ntESCs are severely defective in differentiating into the mesodermal lineage cartilage. Consistently, in a directed in vitro chondrocyte differentiation assay, the cells failed in forming Collagen II expressing cells. These findings underscore the significance in maintaining proper telomere lengths in stem cells and their derivatives for regenerative medicine.
哺乳动物端粒长度主要受端粒酶调控，端粒酶由逆转录酶蛋白（TERT）和 RNA 亚基（）组成。我们之前曾报道过通过体细胞核移植生成小鼠和胚胎干细胞（ntESCs）。在本工作中，我们研究了，和野生型（）ntESCs 的胚层发育能力。端粒长度在野生型中最长，在 ntESCs 中最短，与群体倍增时间呈反向相关。有趣的是，虽然体外胚状体（EB）分化试验揭示了不同基因型 ntESCs 之间 EB 大小的差异，但更严格的体内畸胎瘤试验表明，ntESCs 在向中胚层谱系软骨分化方面存在严重缺陷。一致地，在定向体外软骨细胞分化试验中，细胞未能形成表达 Collagen II 的细胞。这些发现强调了在再生医学中维持干细胞及其衍生物适当端粒长度的重要性。
