Benevento Marco, Tonge Peter D, Puri Mira C, Hussein Samer M I, Cloonan Nicole, Wood David L, Grimmond Sean M, Nagy Andras, Munoz Javier, Heck Albert J R
1] Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Padualaan 8, 3584 CH Utrecht, The Netherlands [2] Netherlands Proteomics Centre, Padualaan 8, 3584 CH Utrecht, The Netherlands.
Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada M5G 1X5.
Nat Commun. 2014 Dec 10;5:5613. doi: 10.1038/ncomms6613.
The ectopic expression of Oct4, Klf4, c-Myc and Sox2 (OKMS) transcription factors allows reprogramming of somatic cells into induced pluripotent stem cells (iPSCs). The reprogramming process, which involves a complex network of molecular events, is not yet fully characterized. Here we perform a quantitative mass spectrometry-based analysis to probe in-depth dynamic proteome changes during somatic cell reprogramming. Our data reveal defined waves of proteome resetting, with the first wave occurring 48 h after the activation of the reprogramming transgenes and involving specific biological processes linked to the c-Myc transcriptional network. A second wave of proteome reorganization occurs in a later stage of reprogramming, where we characterize the proteome of two distinct pluripotent cellular populations. In addition, the overlay of our proteome resource with parallel generated -omics data is explored to identify post-transcriptionally regulated proteins involved in key steps during reprogramming.
Oct4、Klf4、c-Myc和Sox2（OKMS）转录因子的异位表达可使体细胞重编程为诱导多能干细胞（iPSC）。重编程过程涉及复杂的分子事件网络，目前尚未完全明确。在此，我们进行了基于定量质谱的分析，以深入探究体细胞重编程过程中蛋白质组的动态变化。我们的数据揭示了蛋白质组重置的特定阶段，第一阶段发生在重编程转基因激活后48小时，涉及与c-Myc转录网络相关的特定生物学过程。第二阶段的蛋白质组重组发生在重编程的后期，我们对两个不同的多能细胞群体的蛋白质组进行了表征。此外，我们还将蛋白质组资源与平行生成的组学数据进行叠加分析，以识别重编程关键步骤中受转录后调控的蛋白质。
