Accumulation of mtDNA variations in human single CD34+ cells from maternally related individuals: Effects of aging and family genetic background |
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| Authors: | Yong-Gang Yao Sachiko Kajigaya Xingmin Feng Leigh Samsel J Philip McCoy Giuseppe Torelli Neal S Young |
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| Institution: | 1. Hematology Branch and Flow Cytometry Core Facility, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA;2. Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan 650223, China;3. Dipartimento di Oncologia ed Ematologia, Università di Modena e Reggio Emilia, Policlinico, Via del Pozzo 71, Modena 41100, Italy |
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| Abstract: | Marked sequence variation in the mtDNA control region has been observed in human single CD34+ cells, which persist in vivo and are present also in differentiated hematopoietic cells. In this study, we analyzed 5071 single CD34+ cells from 49 individuals (including 31 maternally related members from four families and 18 unrelated donors) in order to determine the mutation spectrum within the mtDNA control region in single cells, as related to aging and family genetic background. Many highly mutated sites among family members were hypervariable sites in the mtDNA control region. Further, CD34+ cells from members of the same family also shared several unique mtDNA variants, suggesting pedigree-specific occurrence of these variants. Overall age-related accumulation of mtDNA mutations in CD34+ cells varied in different families, suggesting a specific accumulation pattern, which might be modulated by family genetic background. Our current findings have implications for the occurrence of mtDNA mutations in hematopoietic stem cells and progenitors. |
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