PUBLICATION

In Vivo imaging of β-cell function reveals glucose-mediated heterogeneity of β-cell functional development

Authors

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.

ID

ZDB-PUB-190130-13

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

Calcineurin/genetics
Calcineurin/metabolism
Glucose/metabolism
Glucose/pharmacology*
Animals, Newborn
Zebrafish
Insulin/metabolism
Gene Expression Regulation, Developmental*
Molecular Imaging/methods*
Stem Cells/cytology
Stem Cells/drug effects
Stem Cells/metabolism
Animals
Insulin-Secreting Cells/cytology
Insulin-Secreting Cells/drug effects*
Insulin-Secreting Cells/metabolism
Mice
Signal Transduction
Cell Differentiation/drug effects
Embryo, Nonmammalian
NFATC Transcription Factors/genetics
NFATC Transcription Factors/metabolism
Single-Cell Analysis/methods*
Pancreas/blood supply
Pancreas/cytology
Pancreas/drug effects*
Pancreas/growth & development

PubMed

30694176 Full text @ Elife

Abstract

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.

Genes / Markers

Figures