Plasticity of calcium signaling cascades in human embryonic stem cell-derived neural precursors

Oksana Forostyak, Nataliya Romanyuk, Alexei Verkhratsky, Eva Sykova, Govindan Dayanithi

    Research output: Contribution to journalArticlepeer-review


    Human embryonic stem cell-derived neural precursors (hESC NPs) are considered to be a promising tool for cell-based therapy in central nervous system injuries and neurodegenerative diseases. The Ca2+ ion is an important intracellular messenger essential for the regulation of various cellular functions. We investigated the role and physiology of Ca2+ signaling to characterize the functional properties of CCTL14 hESC NPs during long-term maintenance in culture (in vitro). We analyzed changes in cytoplasmic Ca2+ concentration ([Ca2+]i) evoked by high K+, adenosine-5′-triphosphate (ATP), glutamate, γ-aminobutyric acid (GABA), and caffeine in correlation with the expression of various neuronal markers in different passages (P6 through P10) during the course of hESC differentiation. We found that only differentiated NPs from P7 exhibited significant and specific [Ca2+]i responses to various stimuli. About 31% of neuronal-like P7 NPs exhibited spontaneous [Ca2+]i oscillations. Pharmacological and immunocytochemical assays revealed that P7 NPs express L- and P/Q-type Ca 2+ channels, P2X2, P2X3, P2X7, and P2Y purinoreceptors, glutamate receptors, and ryanodine (RyR1 and RyR3) receptors. The ATP- and glutamate-induced [Ca2+]i responses were concentration-dependent. Higher glutamate concentrations (over 100 μM) caused cell death. Responses to ATP were observed in the presence or in the absence of extracellular Ca2+. These results emphasize the notion that with time in culture, these cells attain a transient period of operative Ca2+ signaling that is predictive of their ability to act as stem elements. © Copyright 2013, Mary Ann Liebert, Inc. 2013.
    Original languageEnglish
    Pages (from-to)1506-1521
    Number of pages15
    JournalStem Cells and Development
    Issue number10
    Publication statusPublished - 15 May 2013


    • Biological Markers/metabolism
    • Calcium/metabolism
    • Calcium Channels/metabolism
    • *Calcium Signaling/drug effects
    • Cell Count
    • Cell Differentiation/drug effects
    • Embryonic Stem Cells/*cytology/drug effects/*metabolism
    • Glutamates/pharmacology
    • Humans
    • Intracellular Space/drug effects/metabolism
    • Microscopy, Confocal
    • Neural Stem Cells/cytology/drug effects/*metabolism
    • Receptors, Purinergic/metabolism
    • Time Factors


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