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Nature:多能性中的基因表达差异

标签:多能干细胞
摘要 : 虽然人们已经认识到多能干细胞会在不同的子状态之间动态切换,但确定这些状态和主管它们之间的转变的基因调控网络还没有得到很好的界定。George Daley 及同事利用对受到化学和遗传扰动影响的小鼠多能干细胞所进行的单细胞表达分析,确定了转录网络是怎样被动态地重新配置以驱动多能性的不同状态的。

nature13920-f1 

虽然人们已经认识到多能干细胞会在不同的子状态之间动态切换,但确定这些状态和主管它们之间的转变的基因调控网络还没有得到很好的界定。George Daley 及同事利用对受到化学和遗传扰动影响的小鼠多能干细胞所进行的单细胞表达分析,确定了转录网络是怎样被动态地重新配置以驱动多能性的不同状态的。

他们观察到了可以通过细胞分裂遗传的高度差异性,并且还发现,调制微RNA或外部信号传导通道可降低基因表达的异质性和诱导产生一个截然不同的表观遗传状态。

原文摘要:

Deconstructing transcriptional heterogeneity in pluripotent stem cells

Roshan M. Kumar, Patrick Cahan, Alex K. Shalek, Rahul Satija, A. Jay DaleyKeyser, Hu Li,Jin Zhang, Keith Pardee, David Gennert, John J. Trombetta, Thomas C. Ferrante, Aviv Regev, George Q. Daley & James J. Collins

Abstract: Pluripotent stem cells (PSCs) are capable of dynamic interconversion between distinct substates; however, the regulatory circuits specifying these states and enabling transitions between them are not well understood. Here we set out to characterize transcriptional heterogeneity in mouse PSCs by single-cell expression profiling under different chemical and genetic perturbations. Signalling factors and developmental regulators show highly variable expression, with expression states for some variable genes heritable through multiple cell divisions. expression variability and population heterogeneity can be influenced by perturbation of signalling pathways and chromatin regulators. Notably, either removal of mature microRNAs or pharmacological blockage of signalling pathways drives PSCs into a low-noise ground state characterized by a reconfigured pluripotency network, enhanced self-renewal and a distinct chromatin state, an effect mediated by opposing microRNA families acting on the Myc/Lin28/let-7 axis. These data provide insight into the nature of transcriptional heterogeneity in PSCs.(doi: 10.1038/nature13920

对应Nature杂志: 2014年12月04日Nature杂志精选

来源: Nature中文 浏览次数:139

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