新測序方式可檢測單細胞中持續的基因表達譜
作者:
小柯機器人發布時間:2020/8/2 14:32:06
美國賓夕法尼亞大學Arjun Raj團隊利用MemorySeq揭示了與不同細胞行為相關的可遺傳性單細胞基因表達程序。2020年7月30日,《細胞》在線發表了這一成果。
研究人員將Luria和Delbrück的波動分析與基於群體的RNA測序(MemorySeq)相結合,用於鑑定整個轉錄組的基因,其波動可持續存在多個分裂。MemorySeq揭示了多個基因模塊,這些基因模塊在原本同質的克隆群體的稀有細胞中一起表達。
這些罕見的細胞亞群與生物學上不同的行為有關,例如面對抗癌療法的增殖。非遺傳多代波動的鑑定可以揭示單細胞中生物記憶的新形式,並暗示細胞狀態的非遺傳性遺傳力可能是定量的。
據悉,非遺傳因素可導致單個細胞的基因表達水平隨時間大幅波動。尚不清楚這些波動是否可以持續比超過細胞分裂的時間。當前用於測量單細胞中基因表達的方法主要依賴於單個時間點測量,這使得難以測量基因表達波動或細胞記憶的持續時間。
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
Cell:《細胞》,創刊於1974年。隸屬於細胞出版社,最新IF:36.216