利用线粒体的突变实现细胞谱系追踪

2019-04-02  本文已影响0人  蜘蛛鱼

Lineage Tracing in Humans Enabled by Mitochondrial Mutations and Single-Cell Genomics
Ludwig et al., 2019, Cell 176, 1325–1339 March 7, 2019 a 2019 Elsevier Inc. https://doi.org/10.1016/j.cell.2019.01.022

这篇文章讲述的是利用单细胞测序技术(单细胞RNA与单细胞ATAC),线粒体的体细胞突变可以当作天然的barcodes,用来衡量cellular states与clonal dynamics。
已经有报道的学习这些的methods有很多,比如利用heritable markers来得到lineage relationships and cell states. 但是这些都不能用在人类上。人类的lineage-tracing study主要靠检测体细胞突变,比如SNV,CNV以及STR等。用单细胞的whole-genome sequencing来做这件事情不仅很费钱,而且还有很高的错误率。线粒体DNA的好处是突变率比较高,而且基因组也不是很大(省钱)。
作者在这篇文章中对比了很多不同methods的线粒体基因组的覆盖率并做了比较,包括bulk和single-cell的RNA与ATAC sequencing。这是一个很不错的思路,可以把测序文件中产生的线粒体的序列加以好好利用,而不是像之前一样丢弃掉。

文献中一些名词:
Proof-of-principle experiment:Proof of Principle studies are an early stage of clinical drug development when a compound has shown potential in animal models and early safety testing. This step of proof-of-principle (PoP) or proof-of-concept (PoC) often links between Phase-I and dose ranging Phase-II studies. These small-scale studies are designed to detect a signal that the drug is active on a pathophysiologically relevant mechanism, as well as preliminary evidence of efficacy in a clinically relevant endpoint.
Heteroplasmy:Heteroplasmy is the presence of more than one type of organellar genome (mitochondrial DNA or plastid DNA) within a cell or individual. It is an important factor in considering the severity of mitochondrial diseases.
Vatiance decomposition: The variance decomposition indicates the amount of information each variable contributes to the other variables in the autoregression. It determines how much of the forecast error variance of each of the variables can be explained by exogenous shocks to the other variables.

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