Epithelial to mesenchymal transition (EMT) of human stem cell-derived retinal pigment epithelium shares commonalities with malignancy-associated EMT: a proteomic analysis

This study sought to investigate the temporal protein expression changes that occur in a human induced pluripotent stem cell (iPSC)-based RPE-EMT model. We utilized multiplexed isobaric tandem mass tag (TMT) labeling followed by high-resolution tandem mass spectrometry for precise and in-depth quantification of the RPE-EMT proteome. We have identified and quantifed 7,937 protein groups in our TMT-based mass spectrometry analysis. We observed a total of 532 proteins that are differentially regulated during RPE-EMT. Further, we integrated our proteomic data with prior transcriptomic (RNA-seq) data to provide additional insights into RPE-EMT mechanisms. To validate these results, we have performed a label free single shot data-independent acquisition (DIA) mass spectrometry study. Our integrated analysis indicates both the commonality and uniqueness of RPE-EMT compared with malignancy-associated EMT. Our comparative analysis also revealed that multiple AMD-associated risk factors are differentially regulated during RPE-EMT. Together, our integrated dataset provides a comprehensive RPE-EMT atlas and resource for understanding the molecular signaling events and associated biological pathways that underlie RPE-EMT onset. This resource has already facilitated the identification of chemical modulators that could inhibit RPE-EMT, and it will hopefully aid in ongoing efforts to develop EMT inhibition as an approach for the treatment of retinal disease.PMID:34455105 | DOI:10.1016/j.mcpr...
Source: Molecular and Cellular Proteomics : MCP - Category: Molecular Biology Authors: Source Type: research