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Increased expression of 6-phosphofructo-2-kinase/fructose 2,6-bisphosphatase-3 is required for growth of mouse embryonic stem cells that are undergoing differentiation

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Abstract

The unlimited proliferation capacity of embryonic stem cells (ESCs) coupled with their capability to differentiate into several cell types makes them an attractive candidate for studying the molecular mechanisms regulating self-renewal and transition from pluripotent state. Although the roles of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase family (PFKFB1-4) in cell survival, proliferation, and differentiation in tumor cells have been studied, their role in mouse ESC (mESC) biology is currently unkown. In the current study, Pfkfb isoenzyme expressions were analyzed in R1 and J1 mESCs that were cultured in the presence and absence of leukemia inhibitory factor (LIF). We report that expression of the Pfkfb3 isoenzyme was markedly increased when mESCs were promoted to differentiate upon LIF removal. We then demonstrated that Pfkfb3 silencing induced the differentiation marker Brachyury suggesting that Pfkfb3 may be required for the regulation of mesodermal differentiation of mESCs. Furthermore, we show that the increase in Pfkfb3 expression is required for the growth of early differentiated mESCs. Although these results provide important insights into the early differentiation of mESCs with regard to Pfkfb expressions, further mechanistic studies will be needed for understanding the pathways and mechanisms involved in regulation of proliferation and early differentiation of mESCs through Pfkfb3.

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Data availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

This work was supported by the Scientific Research Fund of Bursa Uludag University [grant number# OUAP(V)-2013/27] and Scientific and Technological Research Council of Turkey [grant number#116Z570).

Funding

This study was supported by the Scientific Research Fund of Bursa Uludag University [grant number# OUAP(V)-2013/27] and Scientific and Technological Research Council of Turkey [grant number#116Z570).

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Authors and Affiliations

  1. Department of Biochemistry, School of Veterinary Medicine, Bursa Uludag University, Bursa, Turkey

    Saime Guzel, Tugba Hazal Altunok & Abdullah Yalcin

  2. Research Center for Translational Medicine, Koc University, 34010, Istanbul, Turkey

    Yunus Gurpinar

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  1. Saime Guzel
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  2. Yunus Gurpinar
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  3. Tugba Hazal Altunok
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  4. Abdullah Yalcin
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Contributions

Conceptualization: SG and AY.; Analysis of experiments, data curation: SG, THA and YG.; Funding Acquisition: SG; Writing: SG; Review and Editing: AY.

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Correspondence to Saime Guzel or Abdullah Yalcin.

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Guzel, S., Gurpinar, Y., Altunok, T.H. et al. Increased expression of 6-phosphofructo-2-kinase/fructose 2,6-bisphosphatase-3 is required for growth of mouse embryonic stem cells that are undergoing differentiation. Cytotechnology 75, 27–38 (2023). https://doi.org/10.1007/s10616-022-00557-9

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