In vivo Imaging β-cell Function Reveals Two Waves of β-cell Maturation

Zhao, J.; Zong, W.; Wu, Y.; Shen, J.; Gou, D.; Zhao, Y.; Wu, R.; Niu, F.; Wang, X.; Zheng, X.; Wang, A.; Zhang, Y.; Xiong, J.-W.; Chen, L.; Liu, Y.

doi:10.1101/159673

bioRxiv · 10.1101/159673

In vivo Imaging β-cell Function Reveals Two Waves of β-cell Maturation

Zhao, J.·Zong, W.·Wu, Y.·Shen, J.·Gou, D.·Zhao, Y.·Wu, R.·Niu, F.·Wang, X.·Zheng, X.·Wang, A.·Zhang, Y.·Xiong, J.-W.·Chen, L.·Liu, Y.

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Abstract

The insulin-secreting cells generated from stem cells in vitro are less glucose responsive than primary {beta}-cells. To search for the missing ingredients that are needed for {beta}-cell maturation, we have longitudinally monitored function of every {beta}-cell in Tg (ins:Rcamp1.07) zebrafish embryos with a newly-invented two-photon light-sheet microscope. We have shown that {beta}-cell maturation begins from the islet mantle and propagates to the islet core during the hatching period, coordinated by the islet vascularization. Lower concentration of glucose is optimal to initiate {beta}-cell maturation, while increased glucose delivery to every cell through microcirculation is required for functional boosting of the {beta}-cells. Both the initiation and the boosting of {beta}-cell maturation demands activation of calcineurin/NFAT by glucose. Calcineurin activator combined with glucose promotes mouse neonatal {beta}-cells cultured in vitro to mature to a functional state similar to adult {beta}-cells, suggesting a new strategy for improving stem cell-derived {beta}-like cell function in vitro.

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Zhao, J., Zong, W., Wu, Y., Shen, J., Gou, D., Zhao, Y., Wu, R., Niu, F., Wang, X., Zheng, X., Wang, A., Zhang, Y., Xiong, J.-W., Chen, L., Liu, Y.. 2017-07-05. In vivo Imaging β-cell Function Reveals Two Waves of β-cell Maturation. https://doi.org/10.1101/159673

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