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Quantitative Secretomics Reveals Extrinsic Signals Involved in Human Pluripotent Stem Cell Cardiomyogenesis
Author(s) -
Wolling Hanna,
Konze Sarah A.,
Höfer Anne,
Erdmann Jelena,
Pich Andreas,
Zweigerdt Robert,
Buettner Falk F. R.
Publication year - 2018
Publication title -
proteomics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.26
H-Index - 167
eISSN - 1615-9861
pISSN - 1615-9853
DOI - 10.1002/pmic.201800102
Subject(s) - induced pluripotent stem cell , stem cell , microbiology and biotechnology , biology , computational biology , embryonic stem cell , genetics , gene
Human pluripotent stem cells can be differentiated in vitro into cardiomyocytes (CMs) but the molecular mechanisms behind this process are still not fully understood. In particular, the identification of morphogens remained elusive because the mass spectrometry–based identification of secreted proteins from cell culture supernatants is impeded by high levels of albumin present in common differentiation media. An albumin‐free cardiomyogenic differentiation medium is established in this study and applied for secretomics at seven different time points during in vitro differentiation. By this analysis 4832 proteins are identified with 1802 being significantly altered during differentiation and 431 of these are annotated as secreted. Numerous extrinsic components of Wnt, TGFβ, Activin A, Nodal, BMP, or FGF signaling pathways are quantitatively assessed during differentiation. Notably, the abundance of pathway agonists is generally lower compared to the respective antagonists but their curves of progression over timer were rather similar. It is hypothesized that TGFβ, Activin A, and Nodal signaling are turned down shortly upon the initiation of cardiac differentiation whereas BMP signaling is switched on. Wnt and FGF signaling peaks between d0 and d3 of differentiation, and interestingly, Activin A and TGFβ signaling seem to be reactivated at the cardiac progenitor stages and/or in early CMs.