期刊
REPRODUCTIVE BIOMEDICINE ONLINE
卷 12, 期 1, 页码 101-106出版社
ELSEVIER SCI LTD
DOI: 10.1016/S1472-6483(10)60987-X
关键词
adult stem cells; ageing; embryos; embryonic stein cells; mitochondria; mitochondrial deletions; rhesus macaques
资金
- NCRR NIH HHS [1R21RR021881, R21 RR021881-02, R21 RR021881-01, R21 RR021881-03, R21 RR021881-04, R24RR015395-03] Funding Source: Medline
- NICHD NIH HHS [R03 HD046553-01A1, R01HD045966-01A2, R03 HD046553-02, R03 HD046553-02S1, 01HD045966, R03HD046553-01A1, R03 HD046553-03] Funding Source: Medline
- EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH &HUMAN DEVELOPMENT [R03HD046553, R01HD045966] Funding Source: NIH RePORTER
- NATIONAL CENTER FOR RESEARCH RESOURCES [R24RR015395, R21RR021881] Funding Source: NIH RePORTER
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.
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