Guo Guoji, Pinello Luca, Han Xiaoping, Lai Shujing, Shen Li, Lin Ta-Wei, Zou Keyong, Yuan Guo-Cheng, Orkin Stuart H
Division of Pediatric Hematology/Oncology, Dana Farber Cancer Institute and Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA; Center for Stem Cell and Regenerative Medicine, Zhejiang University School of Medicine, Hangzhou 310058, China.
Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Harvard TH Chan School of Public Health, Boston, MA 02115, USA.
Cell Rep. 2016 Feb 2;14(4):956-965. doi: 10.1016/j.celrep.2015.12.089. Epub 2016 Jan 21.
Variation in gene expression is an important feature of mouse embryonic stem cells (ESCs). However, the mechanisms responsible for global gene expression variation in ESCs are not fully understood. We performed single-cell mRNA-seq analysis of mouse ESCs and uncovered significant heterogeneity in ESCs cultured in serum. We define highly variable gene clusters with distinct chromatin states and show that bivalent genes are prone to expression variation. At the same time, we identify an ESC-priming pathway that initiates the exit from the naive ESC state. Finally, we provide evidence that a large proportion of intracellular network variability is due to the extracellular culture environment. Serum-free culture reduces cellular heterogeneity and transcriptome variation in ESCs.
基因表达的变化是小鼠胚胎干细胞（ESC）的一个重要特征。然而，负责ESC中全局基因表达变化的机制尚未完全了解。我们对小鼠ESC进行了单细胞mRNA测序分析，发现血清培养的ESC中存在显著的异质性。我们定义了具有不同染色质状态的高度可变基因簇，并表明双价基因易于发生表达变化。同时，我们确定了一条启动从幼稚ESC状态退出的ESC启动途径。最后，我们提供证据表明，细胞内网络的很大一部分变异性是由于细胞外培养环境造成的。无血清培养减少了ESC中的细胞异质性和转录组变异。
