Mitochondrial DNA deletions in primate embryonic and adult stem cells
Mitochondrial DNA deletions in primate embryonic and adult stem cells
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DOI：
10.1016/s1472-6483(10)60987-x
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发表时间：
2006-01-01
影响因子：
4
通讯作者：
Brenner, CA
中科院分区：
文献类型：
--
作者：
Gibson, TC;Pei, Y;Brenner, CA
线粒体DNA（mtDNA）突变自然发生在骨骼肌纤维从老年恒河猴。此外，在有生育能力的猴子的生殖囊泡卵母细胞中也观察到mtDNA突变。本研究的目的是确定恒河猴线粒体常见缺失是否存在于体外胚胎生产（IVP）产生的卵母细胞和胚胎以及恒河猴成人和胚胎干细胞系中。在IVP产生的胚胎、三种IVP衍生的胚胎干细胞系（ORMES 1、2和7）、一种体内衍生的胚胎干细胞系（R4）和多次传代的成人骨髓基质细胞（BMSC）系中检测到恒河猴常见缺失。将来自成人脂肪基质细胞（ATSC）系的线粒体DNA与来自用表达端粒酶的逆转录病毒载体ATSC-TERT转染的永生化系的线粒体DNA进行比较。与永生化ATSC-TERT系相比，多次传代的ATSC系具有显着更高水平的恒河猴常见缺失。mtDNA突变在卵母细胞、胚胎和随后的胚胎干细胞系以及成体干细胞系中的积累可能导致线粒体功能障碍，从而损害ATP的产生。作者认为，这一信息为非人类灵长类动物和人类胚胎干细胞技术的平行发展建立了一个令人信服的论据。
Mitochondrial DNA (mtDNA) mutations occur naturally in skeletal muscle fibers from aged rhesus macaques. In addition, mtDNA mutations have been observed in germinal vesicle oocytes from fertile monkeys. The goal of this study was to determine whether the rbesus macaque mitochondrial common deletion was present in oocytes and embryos generated by in-vitro embryo production (IVP), as well as in rhesus adult and embryonic stem cell lines. The rhesus common deletion was detected in IVP-generated embryos, three IVP-derived embryonic stem cell lines (ORMES 1, 2 and 7), one in-vivo-derived embryonic stem cell line (R4) and multiple passages of an adult bone marrow stromal cell (BMSC) line. Mitochondrial DNA from an adult adipose stromal cell (ATSC) line was compared with mtDNA from an immortalized line transfected with a retroviral vector expressing telomerase, ATSC-TERT. Multiple passages of the ATSC line harboured a dramatically higher level of the rhesus common deletion than the immortalized ATSC-TERT line. Accumulation of mtDNA mutations in oocytes, embryos and subsequent embryonic stem cell lines, as well as adult stem cell lines, may contribute to mitochondrial dysfunction, and thereby impair ATP production. The authors believe this information establishes a compelling argument for the parallel development of embryonic stem cell technology in non-human primates and humans.