Inhibition of FGF and TGF-β Pathways in hESCs Identify STOX2 as a Novel SMAD2/4 Cofactor

• Published in: Biology (Basel, Switzerland) Vol. 9; no. 12; p. 470
• Main Authors: Renz, Peter F, Spies, Daniel, Tsikrika, Panagiota, Wutz, Anton, Beyer, Tobias A, Ciaudo, Constance
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 16.12.2020; MDPI
• Subjects: Cell culture; Cloning; Embryo cells; FGF pathway; Fibroblast growth factors; Gene expression; Growth factors; hESCs; Ligands; Long-term effects; Plasmids; Pluripotency; Quality control; Signal transduction; Smad2 protein; Statistical analysis; Stem cells; STOX2; TGF-β pathway; time course differential expression analysis; Transcription; Transcription factors; Transforming growth factor-b; STOX2; FGF pathway; time course differential expression analysis; TGF-β pathway; pluripotency; hESCs
• ISSN: 2079-7737; 2079-7737
• 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.