Dynamic proteomic profiling of extra-embryonic endoderm differentiation in mouse embryonic stem cells
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Claire M Mulvey Christian Schröter Laurent Gatto Duygu Dikicioglu Isik Baris Fidaner Andy Christoforou Michael J Deery Lily TY Cho Kathy Niakan Alfonso Martinez-Arias Kathryn S LilleyAbstract
During mammalian preimplantation development, the cells of the blastocyst's inner cell mass differentiate into the epiblast and primitive endoderm lineages, which give rise to the fetus and extra-embryonic tissues, respectively. Extra-embryonic endoderm (XEN) differentiation can be modeled in vitro by induced expression of GATA transcription factors in mouse embryonic stem cells. Here, we use this GATA-inducible system to quantitatively monitor the dynamics of global proteomic changes during the early stages of this differentiation event and also investigate the fully differentiated phenotype, as represented by embryo-derived XEN cells. Using mass spectrometry-based quantitative proteomic profiling with multivariate data analysis tools, we reproducibly quantified 2,336 proteins across three biological replicates and have identified clusters of proteins characterized by distinct, dynamic temporal abundance profiles. We first used this approach to highlight novel marker candidates of the pluripotent state and XEN differentiation. Through functional annotation enrichment analysis, we have shown that the downregulation of chromatin-modifying enzymes, the reorganization of membrane trafficking machinery, and the breakdown of cell-cell adhesion are successive steps of the extra-embryonic differentiation process. Thus, applying a range of sophisticated clustering approaches to a time-resolved proteomic dataset has allowed the elucidation of complex biological processes which characterize stem cell differentiation and could establish a general paradigm for the investigation of these processes.
Journal details
Journal Stem Cells
Volume 33
Issue number 9
Pages 2712-2725
Available online
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Publisher website (DOI) 10.1002/stem.2067
Europe PubMed Central 26059426
Pubmed 26059426
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