ZFIN ID: ZDB-PUB-190130-13
In Vivo imaging of β-cell function reveals glucose-mediated heterogeneity of β-cell functional development
Zhao, J., Zong, W., Zhao, Y., Gou, D., Liang, S., Shen, J., Wu, Y., Zheng, X., Wu, R., Wang, X., Niu, F., Wang, A., Zhang, Y., Xiong, J.W., Chen, L., Liu, Y.
Date: 2019
Source: eLIFE   8: (Journal)
Registered Authors: Chen, Liangyi, Liu, Yanmei, Xiong, Jing-Wei
Keywords: developmental biology, mouse, regenerative medicine, stem cells, zebrafish
MeSH Terms:
  • Animals
  • Animals, Newborn
  • Calcineurin/genetics
  • Calcineurin/metabolism
  • Cell Differentiation/drug effects
  • Embryo, Nonmammalian
  • Gene Expression Regulation, Developmental*
  • Glucose/metabolism
  • Glucose/pharmacology*
  • Insulin/metabolism
  • Insulin-Secreting Cells/cytology
  • Insulin-Secreting Cells/drug effects*
  • Insulin-Secreting Cells/metabolism
  • Mice
  • Molecular Imaging/methods*
  • NFATC Transcription Factors/genetics
  • NFATC Transcription Factors/metabolism
  • Pancreas/blood supply
  • Pancreas/cytology
  • Pancreas/drug effects*
  • Pancreas/growth & development
  • Signal Transduction
  • Single-Cell Analysis/methods*
  • Stem Cells/cytology
  • Stem Cells/drug effects
  • Stem Cells/metabolism
  • Zebrafish
PubMed: 30694176 Full text @ Elife
How pancreatic β-cells acquire function in vivo is a long-standing mystery due to the lack of technology to visualize β-cell function in living animals. Here, we applied a high-resolution two-photon light-sheet microscope for the first in vivo imaging of Ca2+ activity of every β-cell in Tg (ins:Rcamp1.07) zebrafish. We reveal that the heterogeneity of β-cell functional development in vivo occurred as two waves propagating from the islet mantle to the core, coordinated by islet vascularization. Increasing amounts of glucose induced functional acquisition and enhancement of β-cells via activating calcineurin/nuclear factor of activated T-cells (NFAT) signalling. Conserved in mammalians, calcineurin/NFAT prompted high-glucose-stimulated insulin secretion of neonatal mouse islets cultured in vitro. However, the reduction in low-glucose-stimulated insulin secretion was dependent on optimal glucose but independent of calcineurin/NFAT. Thus, combination of optimal glucose and calcineurin activation represents a previously unexplored strategy for promoting functional maturation of stem cell-derived β-like cells in vitro.