Tyrosine Kinase Expressed in Hepatocellular Carcinoma, TEC, Controls Pluripotency and Early Cell Fate Decisions of Human Pluripotent Stem Cells via Regulation of Fibroblast Growth Factor-2 Secretion.
Stem Cells. 2017-07-06; 35(9): 2050-2059
DOI: 10.1002/stem.2660
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Vanova T(1), Konecna Z(1), Zbonakova Z(1), La Venuta G(2), Zoufalova K(1)(3), Jelinkova S(1), Varecha M(1)(3), Rotrekl V(1)(3), Krejci P(1)(3), Nickel W(2),
Dvorak P(1)(2), Kunova Bosakova M(1).
Author information:
(1)Department of Biology, Faculty of Medicine, Masaryk University, Brno, Czech Republic.
(2)Heidelberg University Biochemistry Center (BZH), Heidelberg, Germany.
(3)International Clinical Research Center, St. Anne’s University Hospital, Brno, Czech Republic.
Human pluripotent stem cells (hPSC) require signaling provided by fibroblast
growth factor (FGF) receptors. This can be initiated by the recombinant FGF2
ligand supplied exogenously, but hPSC further support their niche by secretion of
endogenous FGF2. In this study, we describe a role of tyrosine kinase expressed
in hepatocellular carcinoma (TEC) kinase in this process. We show that
TEC-mediated FGF2 secretion is essential for hPSC self-renewal, and its lack
mediates specific differentiation. Following both short hairpin RNA- and small
interfering RNA-mediated TEC knockdown, hPSC secretes less FGF2. This impairs
hPSC proliferation that can be rescued by increasing amounts of recombinant FGF2.
TEC downregulation further leads to a lower expression of the pluripotency
markers, an improved priming towards neuroectodermal lineage, and a failure to
develop cardiac mesoderm. Our data thus demonstrate that TEC is yet another
regulator of FGF2-mediated hPSC pluripotency and differentiation. Stem Cells
2017;35:2050-2059.
© 2017 AlphaMed Press.