Percharde Michelle, Wong Priscilla, Ramalho-Santos Miguel
Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, Center for Reproductive Sciences, University of California, San Francisco, San Francisco, CA 94143, USA.
Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, Center for Reproductive Sciences, University of California, San Francisco, San Francisco, CA 94143, USA; Caribou Biosciences, Berkeley, California 94710, USA.
Cell Rep. 2017 Jun 6;19(10):1987-1996. doi: 10.1016/j.celrep.2017.05.036.
Primordial germ cells (PGCs) are vital for inheritance and evolution. Their transcriptional program has been extensively studied and is assumed to be well known. We report here a remarkable global upregulation of the transcriptome of mouse PGCs compared to somatic cells. Using cell-number-normalized genome-wide analyses, we uncover significant transcriptional amplification in PGCs, including mRNAs, rRNA, and transposable elements. Hypertranscription preserves tissue-specific gene expression patterns, correlates with cell size, and can still be detected in E15.5 male germ cells when proliferation has ceased. PGC hypertranscription occurs at the level of nascent transcription, is accompanied by increased translation rates, and is driven by Myc factors n-Myc and l-Myc (but not c-Myc) and by P-TEFb. This study provides a paradigm for transcriptional analyses during development and reveals a major global hyperactivity of the germline transcriptome.
原始生殖细胞(PGCs)对于遗传和进化至关重要。它们的转录程序已得到广泛研究,并且被认为是广为人知的。我们在此报告,与体细胞相比,小鼠PGCs的转录组有显著的整体上调。通过细胞数量标准化的全基因组分析,我们发现PGCs中存在显著的转录扩增,包括mRNA、rRNA和转座元件。超转录保留了组织特异性基因表达模式,与细胞大小相关,并且在增殖停止后的E15.5雄性生殖细胞中仍可检测到。PGCs超转录发生在新生转录水平,伴随着翻译速率的增加,并由Myc因子n-Myc和l-Myc(而非c-Myc)以及P-TEFb驱动。这项研究为发育过程中的转录分析提供了一个范例,并揭示了生殖系转录组的一个主要的整体高活性。