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单细胞线粒体测序揭示了自然衰老小鼠的低频线粒体突变

Fuyan Liu¹, Xiaolin Sun¹, Cai Wei¹

¹BGI Research, Beijing, China.

|October 18, 2024

概括

这项研究引入了C4_mtscATAC-seq,这是单细胞线粒体测序的新方法. 它揭示了与年龄相关的线粒体DNA变异及其与小鼠组织基因活性的联系.

科学领域:

基因组学就是基因组学.
分子生物学分子生物学
细胞生物学细胞生物学

背景情况:

线粒体对于细胞功能至关重要,但它们在单细胞水平上的异质性仍未得到充分研究.
目前在单细胞分辨率下分析线粒体DNA (mtDNA) 的方法有限.

研究的目的:

优化和验证一种新的单细胞线粒体测序工作流程 (C4_mtscATAC-seq).
研究与年龄相关的mtDNA含量变化和小鼠组织突变.
探索mtDNA变异与核基因表达之间的关系.

主要方法:

优化DNBelabC4单细胞ATAC测序工作流程用于线粒体测序 (C4_mtscATAC-seq).
用于协议验证的HEK-293T细胞的测序.
应用C4_mtscATAC-seq在年轻和老年小鼠的脏和骨髓组织上.

主要成果:

C4_mtscATAC-seq同时成功捕获了线粒体含量和开放色素状态.
与老年组织相比,年轻的小鼠组织显示出较高的mtDNA含量和相关的核基因活性.
衰老的组织表现出更多的mtDNA突变,变异性等位基因频率增加 (VAF),包括特定变异 (m.9821A>T,m.15219T>C,m.15984C>T).
差异开放色素分析将特定的mtDNA变异与KLF15和NRF1.1等转录因子联系起来.

结论:

C4_mtscATAC-seq为单细胞线粒体测序提供了一个有价值的替代方案.
这项研究提供了有关年龄的线粒体变异及其对细胞功能的潜在影响的见解.
已识别的mtDNA变异可能会影响核基因调节,为未来的研究提供目标.

关键词:

ATAC ATAC ATAC ATAC ATAC ATAC ATAC ATAC ATAC ATAC ATAC ATAC ATAC ATAC ATAC ATAC ATAC ATAC ATAC ATAC ATAC ATAC 衰老的衰老衰老的衰老线粒体DNA (mtDNA) 是指线粒体的DNA.这是线粒体突变.一个单细胞测序.

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