Renz Peter F, Spies Daniel, Tsikrika Panagiota, Wutz Anton, Beyer Tobias A, Ciaudo Constance
Department of Biology, Swiss Federal Institute of Technology Zurich, Institute of Molecular Health Sciences, Otto-Stern Weg 7, CH-8093 Zurich, Switzerland.
Molecular Life Science Program, Life Science Zurich Graduate School, Institute of Molecular Life Sciences, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland.
Biology (Basel). 2020 Dec 16;9(12):470. doi: 10.3390/biology9120470.
The fibroblast growth factor (FGF) and the transforming growth factor-β (TGF-β) pathways are both involved in the maintenance of human embryonic stem cells (hESCs) and regulate the onset of their differentiation. Their converging functions have suggested that these pathways might share a wide range of overlapping targets. Published studies have focused on the long-term effects (24-48 h) of FGF and TGF-β inhibition in hESCs, identifying direct and indirect target genes. In this study, we focused on the earliest transcriptome changes occurring between 3 and 9 h after FGF and TGF-β inhibition to identify direct target genes only. Our analysis clearly shows that only a handful of target transcripts are common to both pathways. This is surprising in light of the previous literature, and has implications for models of cell signaling in human pluripotent cells. In addition, we identified STOX2 as a novel primary target of the TGF-β signaling pathway. We show that STOX2 might act as a novel SMAD2/4 cofactor. Taken together, our results provide insights into the effect of cell signaling on the transcription profile of human pluripotent cells.
成纤维细胞生长因子（FGF）和转化生长因子-β（TGF-β）信号通路均参与人类胚胎干细胞（hESCs）的维持，并调节其分化起始。它们的共同作用表明，这些信号通路可能共享大量重叠的靶标。已发表的研究聚焦于FGF和TGF-β抑制对hESCs的长期影响（24 - 48小时），鉴定出直接和间接靶基因。在本研究中，我们聚焦于FGF和TGF-β抑制后3至9小时内最早发生的转录组变化，仅鉴定直接靶基因。我们的分析清楚地表明，两条信号通路仅有少数共同的靶转录本。鉴于先前的文献，这一结果令人惊讶，并对人类多能细胞中的细胞信号传导模型具有启示意义。此外，我们鉴定出STOX2是TGF-β信号通路的一个新的主要靶标。我们表明，STOX2可能作为一种新的SMAD2/4辅因子发挥作用。综上所述，我们的结果为细胞信号传导对人类多能细胞转录谱的影响提供了见解。
