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单细胞中基因表达与基因组突变的相关性。

Correlation of gene expression and genome mutation in single B-cells.

机构信息

Biophysics Program, Stanford University, Stanford, California, United States of America.

出版信息

PLoS One. 2013 Jun 28;8(6):e67624. doi: 10.1371/journal.pone.0067624. Print 2013.

Abstract

High-throughput measurement of gene-expression and immune receptor repertoires have recently become powerful tools in the study of adaptive immune response. However, despite their now-widespread use, both tend to discard cell identity by treating cell populations in bulk, and therefore lose the correlation between genetic variability and gene-expression at the single cell level. In order to recover this information, we developed a method to simultaneously measure gene expression profiles and genome mutations in single cells. We applied this method by quantifying the relationships between gene expression and antibody mutation in ensembles of individual B-cells from immunized mice. The results reveal correlations reflecting the manner in which information propagates between a B-cell's antigen receptors, its gene expression, and its mutagenic machinery, and demonstrate the power of this approach to illuminate both heterogeneity and physiology in cell populations.

摘要

高通量测量基因表达和免疫受体库最近已成为研究适应性免疫反应的有力工具。然而,尽管它们现在已经得到广泛应用,但这两种方法都倾向于通过批量处理细胞群体来丢弃细胞身份,从而丧失了单细胞水平上遗传变异性和基因表达之间的相关性。为了恢复这些信息,我们开发了一种同时测量单细胞中基因表达谱和基因组突变的方法。我们通过量化免疫小鼠个体 B 细胞群体中基因表达和抗体突变之间的关系来应用这种方法。结果揭示了反映信息在 B 细胞的抗原受体、其基因表达和其诱变机制之间传播方式的相关性,并展示了这种方法阐明细胞群体异质性和生理学的强大能力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/99de/3695916/1b0907731bd4/pone.0067624.g001.jpg

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