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TEC-mediated FGF2 Secretion Controls hPSC Pluripotency

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Review of “TEC controls pluripotency and early cell fate decisions of human pluripotent stem cells via regulation of FGF2 secretion” from STEM CELLS by Stuart P. Atkinson

Signaling from basic fibroblast growth factor receptors (FGFRs) promotes the growth and pluripotent nature of human pluripotent stem cells (hPSCs), thereby allowing their extended in vitro cultivation. Either as part of the exogenously added culture medium or secreted from hPSCs themselves, basic fibroblast growth factor (FGF)-2 can bind to FGFRs to activate the MAPK and PI3K/AKT pathways that kick-start the pluripotency program. 

Multiple known factors control the secretion of FGF2, but researchers from the laboratories of Petr Dvorak and Michaela Kunova Bosáková (Masaryk University, Brno, Czech Republic) have recently focused on a novel target. In a new STEM CELLS study, Vanova et al. now demonstrate that TEC (or tyrosine kinase expressed in hepatocellular carcinoma )[1] represents a novel regulator of FGF2-mediated hPSC pluripotency [2].

Previous studies indicated that direct interaction of TEC with FGF2, resulting in Tyr82 phosphorylation [1], regulated FGF2 secretion. In this new study, the authors detected high TEC expression in undifferentiated hPSCs and during early stages of differentiation, leading to TEC-FGF2 interaction and the phosphorylation of a low molecular weight variant of FGF2, whose secretion activates autocrine/paracrine FGF signaling to promote pluripotency [3]. However, TEC also promoted the phosphorylation a high molecular weight variant of FGF2 in hPSCs [4, 5]. 

Interestingly, TEC knockdown in hPSCs resulted in significantly lower FGF2 secretion and this, in turn, impaired the proliferation and self-renewal capacity of the affected hPSCs and prompted differentiation. However, the loss of TEC boosted differentiation preferably to neural lineage at the expense of cardiac/mesodermal differentiation, suggesting the involvement of TEC in early neuroectodermal/mesendodermal fate decisions.

This new study identifies TEC as an essential part of the FGF2-mediated pluripotency machinery and further widens our knowledge base on the maintenance of pluripotency in human cells. Keep the Stem Cells Portal a click away to keep in touch with all the new pluripotency-associated factors!

References

  1. Ebert AD, Laussmann M, Wegehingel S, et al. Tec-kinase-mediated phosphorylation of fibroblast growth factor 2 is essential for unconventional secretion. Traffic 2010;11:813-826.
  2. Vanova T, Konecna Z, Zbonakova Z, et al. 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;35:2050-2059.
  3. Florkiewicz RZ, Majack RA, Buechler RD, et al. Quantitative export of FGF-2 occurs through an alternative, energy-dependent, non-ER/Golgi pathway. J Cell Physiol 1995;162:388-399.
  4. Dvorak P, Dvorakova D, Koskova S, et al. Expression and potential role of fibroblast growth factor 2 and its receptors in human embryonic stem cells. Stem Cells 2005;23:1200-1211.
  5. Eiselleova L, Matulka K, Kriz V, et al. A complex role for FGF-2 in self-renewal, survival, and adhesion of human embryonic stem cells. Stem Cells 2009;27:1847-1857.