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
Jazyk angličtina Země Velká Británie, Anglie Médium print-electronic
Typ dokumentu časopisecké články
PubMed
28631381
DOI
10.1002/stem.2660
Knihovny.cz E-zdroje
- Klíčová slova
- Cardiac differentiation, Embryonic stem cells, Fibroblast growth factor, Fibroblast growth factor 2, Neural differentiation, Pluripotent stem cells, Tyrosine kinase expressed in hepatocellular carcinoma,
- MeSH
- biologické markery metabolismus MeSH
- buněčné linie MeSH
- buněčný rodokmen * účinky léků MeSH
- down regulace účinky léků MeSH
- fibroblastový růstový faktor 2 metabolismus MeSH
- lidé MeSH
- pluripotentní kmenové buňky cytologie enzymologie MeSH
- proliferace buněk účinky léků MeSH
- rekombinantní proteiny farmakologie MeSH
- tyrosinkinasy metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- biologické markery MeSH
- fibroblastový růstový faktor 2 MeSH
- rekombinantní proteiny MeSH
- Tec protein-tyrosine kinase MeSH Prohlížeč
- tyrosinkinasy MeSH
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.
Department of Biology Faculty of Medicine Masaryk University Brno Czech Republic
Heidelberg University Biochemistry Center Heidelberg Germany
International Clinical Research Center St Anne's University Hospital Brno Czech Republic
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