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新测序方式可检测单细胞中持续的基因表达谱
作者:小柯机器人 发布时间:2020/8/2 14:32:06

美国宾夕法尼亚大学Arjun Raj团队利用MemorySeq揭示了与不同细胞行为相关的可遗传性单细胞基因表达程序。2020年7月30日,《细胞》在线发表了这一成果。

研究人员将Luria和Delbrück的波动分析与基于群体的RNA测序(MemorySeq)相结合,用于鉴定整个转录组的基因,其波动可持续存在多个分裂。MemorySeq揭示了多个基因模块,这些基因模块在原本同质的克隆群体的稀有细胞中一起表达。
 
这些罕见的细胞亚群与生物学上不同的行为有关,例如面对抗癌疗法的增殖。非遗传多代波动的鉴定可以揭示单细胞中生物记忆的新形式,并暗示细胞状态的非遗传性遗传力可能是定量的。
 
据悉,非遗传因素可导致单个细胞的基因表达水平随时间大幅波动。尚不清楚这些波动是否可以持续比超过细胞分裂的时间。当前用于测量单细胞中基因表达的方法主要依赖于单个时间点测量,这使得难以测量基因表达波动或细胞记忆的持续时间。
 
附:英文原文

Title: Memory Sequencing Reveals Heritable Single-Cell Gene Expression Programs Associated with Distinct Cellular Behaviors

Author: Sydney M. Shaffer, Benjamin L. Emert, Raúl A. Reyes Hueros, Christopher Cote, Guillaume Harmange, Dylan L. Schaff, Ann E. Sizemore, Rohit Gupte, Eduardo Torre, Abhyudai Singh, Danielle S. Bassett, Arjun Raj

Issue&Volume: 2020-07-30

Abstract: Non-genetic factors can cause individual cells to fluctuate substantially in geneexpression levels over time. It remains unclear whether these fluctuations can persistfor much longer than the time of one cell division. Current methods for measuringgene expression in single cells mostly rely on single time point measurements, makingthe duration of gene expression fluctuations or cellular memory difficult to measure.Here, we combined Luria and Delbrück’s fluctuation analysis with population-basedRNA sequencing (MemorySeq) for identifying genes transcriptome-wide whose fluctuationspersist for several divisions. MemorySeq revealed multiple gene modules that expressedtogether in rare cells within otherwise homogeneous clonal populations. These rarecell subpopulations were associated with biologically distinct behaviors like proliferationin the face of anti-cancer therapeutics. The identification of non-genetic, multigenerationalfluctuations can reveal new forms of biological memory in single cells and suggeststhat non-genetic heritability of cellular state may be a quantitative property.

DOI: 10.1016/j.cell.2020.07.003

Source: https://www.cell.com/cell/fulltext/S0092-8674(20)30868-0

期刊信息
Cell:《细胞》,创刊于1974年。隶属于细胞出版社,最新IF:36.216
官方网址:https://www.cell.com/