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

Int J Mol Sci. 2019 Nov 30;20(23):6037. doi: 10.3390/ijms20236037.


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.

Keywords: cardiac progenitor cells; fibroblast growth factor 16; fibroblast growth factors; human secretome; phenotypic screening.

MeSH terms

  • Animals
  • CHO Cells
  • Cell Differentiation / drug effects
  • Cell Proliferation / drug effects*
  • Cricetulus
  • Female
  • Fibroblast Growth Factors / classification
  • Fibroblast Growth Factors / genetics*
  • Fibroblast Growth Factors / metabolism
  • Fibroblast Growth Factors / pharmacology
  • Fibroblasts / cytology
  • Fibroblasts / metabolism
  • Gene Expression
  • Gene Library
  • High-Throughput Screening Assays
  • Humans
  • Induced Pluripotent Stem Cells / cytology
  • Induced Pluripotent Stem Cells / drug effects*
  • Induced Pluripotent Stem Cells / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Myocytes, Cardiac / cytology
  • Myocytes, Cardiac / drug effects*
  • Myocytes, Cardiac / metabolism
  • Primary Cell Culture


  • FGF16 protein, human
  • Fibroblast Growth Factors