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 - PubMed (original) (raw)

. 2017 Sep;35(9):2050-2059.

doi: 10.1002/stem.2660. Epub 2017 Jul 6.

Zaneta Konecna 1, Zuzana Zbonakova 1, Giuseppe La Venuta 2, Karolina Zoufalova 1 3, Sarka Jelinkova 1, Miroslav Varecha 1 3, Vladimir Rotrekl 1 3, Pavel Krejci 1 3, Walter Nickel 2, Petr Dvorak 1 2, Michaela Kunova Bosakova 1

Affiliations

• PMID: 28631381
• DOI: 10.1002/stem.2660

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

Tereza Vanova et al. Stem Cells. 2017 Sep.

Abstract

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.

Keywords: Cardiac differentiation; Embryonic stem cells; Fibroblast growth factor; Fibroblast growth factor 2; Neural differentiation; Pluripotent stem cells; Tyrosine kinase expressed in hepatocellular carcinoma.

© 2017 AlphaMed Press.

PubMed Disclaimer

Similar articles

• Small Molecule Inhibitors Targeting Tec Kinase Block Unconventional Secretion of Fibroblast Growth Factor 2.
  La Venuta G, Wegehingel S, Sehr P, Müller HM, Dimou E, Steringer JP, Grotwinkel M, Hentze N, Mayer MP, Will DW, Uhrig U, Lewis JD, Nickel W. La Venuta G, et al. J Biol Chem. 2016 Aug 19;291(34):17787-803. doi: 10.1074/jbc.M116.729384. Epub 2016 Jul 5. J Biol Chem. 2016. PMID: 27382052 Free PMC article.
• FGF2 secreting human fibroblast feeder cells: a novel culture system for human embryonic stem cells.
  Saxena S, Hanwate M, Deb K, Sharma V, Totey S. Saxena S, et al. Mol Reprod Dev. 2008 Oct;75(10):1523-32. doi: 10.1002/mrd.20895. Mol Reprod Dev. 2008. PMID: 18318041
• Tec-kinase-mediated phosphorylation of fibroblast growth factor 2 is essential for unconventional secretion.
  Ebert AD, Laussmann M, Wegehingel S, Kaderali L, Erfle H, Reichert J, Lechner J, Beer HD, Pepperkok R, Nickel W. Ebert AD, et al. Traffic. 2010 Jun;11(6):813-26. doi: 10.1111/j.1600-0854.2010.01059.x. Epub 2010 Mar 10. Traffic. 2010. PMID: 20230531
• The Startling Properties of Fibroblast Growth Factor 2: How to Exit Mammalian Cells without a Signal Peptide at Hand.
  La Venuta G, Zeitler M, Steringer JP, Müller HM, Nickel W. La Venuta G, et al. J Biol Chem. 2015 Nov 6;290(45):27015-27020. doi: 10.1074/jbc.R115.689257. Epub 2015 Sep 28. J Biol Chem. 2015. PMID: 26416892 Free PMC article. Review.
• Model systems for studying trophoblast differentiation from human pluripotent stem cells.
  Ezashi T, Telugu BP, Roberts RM. Ezashi T, et al. Cell Tissue Res. 2012 Sep;349(3):809-24. doi: 10.1007/s00441-012-1371-2. Epub 2012 Mar 17. Cell Tissue Res. 2012. PMID: 22427062 Free PMC article. Review.

Cited by

• Understanding Gene Involvement in Hepatocellular Carcinoma: Implications for Gene Therapy and Personalized Medicine.
  Younis MA, Harashima H. Younis MA, et al. Pharmgenomics Pers Med. 2024 May 7;17:193-213. doi: 10.2147/PGPM.S431346. eCollection 2024. Pharmgenomics Pers Med. 2024. PMID: 38737776 Free PMC article. Review.
• Characterization of novel CTNNB1 mutation in Craniopharyngioma by whole-genome sequencing.
  He J, Zeng Z, Wang Y, Deng J, Tang X, Liu F, Huang J, Chen H, Liang R, Zan X, Liu Z, Tong A, Guo G, Xu J, Zhu X, Zhou L, Peng Y. He J, et al. Mol Cancer. 2021 Dec 18;20(1):168. doi: 10.1186/s12943-021-01468-7. Mol Cancer. 2021. PMID: 34922552 Free PMC article.
• Regulation of ciliary function by fibroblast growth factor signaling identifies FGFR3-related disorders achondroplasia and thanatophoric dysplasia as ciliopathies.
  Kunova Bosakova M, Varecha M, Hampl M, Duran I, Nita A, Buchtova M, Dosedelova H, Machat R, Xie Y, Ni Z, Martin JH, Chen L, Jansen G, Krakow D, Krejci P. Kunova Bosakova M, et al. Hum Mol Genet. 2018 Mar 15;27(6):1093-1105. doi: 10.1093/hmg/ddy031. Hum Mol Genet. 2018. PMID: 29360984 Free PMC article.
• Role of Non Receptor Tyrosine Kinases in Hematological Malignances and its Targeting by Natural Products.
  Siveen KS, Prabhu KS, Achkar IW, Kuttikrishnan S, Shyam S, Khan AQ, Merhi M, Dermime S, Uddin S. Siveen KS, et al. Mol Cancer. 2018 Feb 19;17(1):31. doi: 10.1186/s12943-018-0788-y. Mol Cancer. 2018. PMID: 29455667 Free PMC article. Review.

MeSH terms

Substances

LinkOut - more resources

• Full Text Sources

  • Ovid Technologies, Inc.
  • Silverchair Information Systems

• Other Literature Sources

  • scite Smart Citations

• Molecular Biology Databases

  • GlyGen glycoinformatics resource