Generation and gene expression profiling of 48 transcription-factor-inducible mouse embryonic stem cell lines.
Generation and gene expression profiling of 48 transcription-factor-inducible mouse embryonic stem cell lines.
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DOI：
10.1038/srep25667
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发表时间：
2016-05-06
影响因子：
4.6
通讯作者：
Ko MS
中科院分区：
文献类型：
--
作者：
Yamamizu K;Sharov AA;Piao Y;Amano M;Yu H;Nishiyama A;Dudekula DB;Schlessinger D;Ko MS
小鼠胚胎干细胞(ESCs)在体外可以分化为多种类型的细胞，为系统研究转录因子在细胞分化中的作用提供了一个理想的平台。在此之前，我们已经建立并分析了137个Tf诱导的小鼠ESC系。作为这个“NIA小鼠ESC库”的扩展，我们另外产生并鉴定了48个小鼠ESC系，其中每个系中的单个TF可以以多西环素可控的方式被诱导。连同以前的ESC线，该库现在包括185条可操控的ESC线(占所有鼠标TF的10%)。全球基因表达谱(转录组)显示，单独的转录因子在小鼠ESCs中诱导48 小时后，其转录朝着特定的分化命运转变(例如，Myt1Isl1和St18的神经谱系；Pitx1、Pitx2、Barhl2和Lmx1a的中胚层谱系；Myb、ETV2和Tbx6的白细胞；以及Pitx1、Pitx2和Dmrtc2的卵巢)。这些数据还提供了推测的每个转铁蛋白的靶基因和这些转铁蛋白的可能功能的列表。这些结果表明，小鼠胚胎干细胞系及其转录组数据对于了解细胞分化的机制和转录因子的功能是有用的。
Mouse embryonic stem cells (ESCs) can differentiate into a wide range – and possibly all cell types in vitro, and thus provide an ideal platform to study systematically the action of transcription factors (TFs) in cell differentiation. Previously, we have generated and analyzed 137 TF-inducible mouse ESC lines. As an extension of this “NIA Mouse ESC Bank,” we generated and characterized 48 additional mouse ESC lines, in which single TFs in each line could be induced in a doxycycline-controllable manner. Together, with the previous ESC lines, the bank now comprises 185 TF-manipulable ESC lines (>10% of all mouse TFs). Global gene expression (transcriptome) profiling revealed that the induction of individual TFs in mouse ESCs for 48 hours shifts their transcriptomes toward specific differentiation fates (e.g., neural lineages by Myt1 Isl1, and St18; mesodermal lineages by Pitx1, Pitx2, Barhl2, and Lmx1a; white blood cells by Myb, Etv2, and Tbx6, and ovary by Pitx1, Pitx2, and Dmrtc2). These data also provide and lists of inferred target genes of each TF and possible functions of these TFs. The results demonstrate the utility of mouse ESC lines and their transcriptome data for understanding the mechanism of cell differentiation and the function of TFs.