Next Article in Journal
PatJAZ6 Acts as a Repressor Regulating JA-Induced Biosynthesis of Patchouli Alcohol in Pogostemon Cablin
Previous Article in Journal
Heterogeneous Pattern of Dependence on Anti-Apoptotic BCL-2 Family Proteins upon CHOP Treatment in Diffuse Large B-Cell Lymphoma
Previous Article in Special Issue
Modelling Neurotropic Flavivirus Infection in Human Induced Pluripotent Stem Cell-Derived Systems
Open AccessArticle

Phenotypic Screen with the Human Secretome Identifies FGF16 as Inducing Proliferation of iPSC-Derived Cardiac Progenitor Cells

1
Bioscience Cardiovascular, Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceutical R&D, AstraZeneca, Gothenburg, 43150 Mölndal, Sweden
2
Mechanistic Biology and Profiling, Discovery Sciences, R&D, AstraZeneca, Gothenburg, 43150 Mölndal, Sweden
3
Quantitative Biology, Discovery Sciences, R&D, AstraZeneca, Cambridge CB40WG, UK
4
Discovery Biology, Discovery Sciences, R&D, AstraZeneca, Gothenburg, 43150 Mölndal, Sweden
5
Discovery Biology, Discovery Sciences, R&D, AstraZeneca, Cambridge CB40WG, UK
6
Structure and Biophysics and Fragment screening, Discovery Sciences, R&D, AstraZeneca, Gothenburg, 43150 Mölndal, Sweden
7
Attana AB, 11419 Stockholm, Sweden
8
Department of Protein Science, School of engineering Sciences in Chemistry, Biotechnology and Health, KTH-Royal Institute of Technology, 11421 Stockholm, Sweden
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(23), 6037; https://doi.org/10.3390/ijms20236037
Received: 24 September 2019 / Revised: 22 November 2019 / Accepted: 27 November 2019 / Published: 30 November 2019
(This article belongs to the Special Issue Disease Modeling Using Human Induced Pluripotent Stem Cells 2.0)
Paracrine factors can induce cardiac regeneration and repair post myocardial infarction by stimulating proliferation of cardiac cells and inducing the anti-fibrotic, antiapoptotic, and immunomodulatory effects of angiogenesis. Here, we screened a human secretome library, consisting of 923 growth factors, cytokines, and proteins with unknown function, in a phenotypic screen with human cardiac progenitor cells. The primary readout in the screen was proliferation measured by nuclear count. From this screen, we identified FGF1, FGF4, FGF9, FGF16, FGF18, and seven additional proteins that induce proliferation of cardiac progenitor cells. FGF9 and FGF16 belong to the same FGF subfamily, share high sequence identity, and are described to have similar receptor preferences. Interestingly, FGF16 was shown to be specific for proliferation of cardiac progenitor cells, whereas FGF9 also proliferated human cardiac fibroblasts. Biosensor analysis of receptor preferences and quantification of receptor abundances suggested that FGF16 and FGF9 bind to different FGF receptors on the cardiac progenitor cells and cardiac fibroblasts. FGF16 also proliferated naïve cardiac progenitor cells isolated from mouse heart and human cardiomyocytes derived from induced pluripotent cells. Taken together, the data suggest that FGF16 could be a suitable paracrine factor to induce cardiac regeneration and repair. View Full-Text
Keywords: human secretome; phenotypic screening; cardiac progenitor cells; fibroblast growth factors; fibroblast growth factor 16 human secretome; phenotypic screening; cardiac progenitor cells; fibroblast growth factors; fibroblast growth factor 16
Show Figures

Graphical abstract

MDPI and ACS Style

Jennbacken, K.; Wågberg, F.; Karlsson, U.; Eriksson, J.; Magnusson, L.; Chimienti, M.; Ricchiuto, P.; Bernström, J.; Ding, M.; Ross-Thriepland, D.; Xue, Y.; Peiris, D.; Aastrup, T.; Tegel, H.; Hober, S.; Sivertsson, Å.; Uhlén, M.; Strömstedt, P.-E.; Davies, R.; Holmberg Schiavone, L. Phenotypic Screen with the Human Secretome Identifies FGF16 as Inducing Proliferation of iPSC-Derived Cardiac Progenitor Cells. Int. J. Mol. Sci. 2019, 20, 6037.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop