Abstract

Neural stem/progenitor cells (NSPCs) are self-renewing, multipotent cells located in the embryonic and adult central nervous system (CNS). Extensive preclinical and clinical studies have shed light on the potential of stem cell replacement therapy for various neurodegenerative diseases. The key prerequisite for the success of these clinical applications is the procurement of a sufficient number of high-quality NSPCs. In this study, we explored the biological activity of Quadrella incana leaf in NSPC homeostasis. We showed that the leaf extract of Quadrella incana upregulated NSPC marker and proliferative potential. On the other hand, Quadrella incana leaf suppressed spontaneous unintended NSPC differentiation. Mechanistically, Quadrella incana leaf contributed to the maintenance of NSPCs by upregulating glycolytic flux and redox potential.

Highlights

  • Neural stem/progenitor cells (NSPCs) are undifferentiated, multipotent cells originating in the embryonic and adult central nervous system (CNS)

  • NSPCs are multipotent cells that differentiate into neurons, astrocytes, and oligodendrocytes, E10.5 NSPCs give rise to neurons, not glial cells, after short-term culturing

  • Given the importance of glycolytic flux and redox balance in the proliferation and stemness of NSPCs, we showed that Quadrella incana leaf extract contributed to the maintenance of NSPCs by upregulating glycolysis and redox potential (Supplementary Fig 6)

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Summary

Introduction

Neural stem/progenitor cells (NSPCs) are undifferentiated, multipotent cells originating in the embryonic and adult central nervous system (CNS). Constitutive expression of the core glycolytic genes, HK2 and LDHA, was found to induce neuronal cell death, suggesting that blockade of glycolytic flux is critical for proper neuronal differentiation and survival [9] Another important feature governing NSPC maintenance is resistance towards oxidative stress. While signaling molecules that promoted NSPC selfrenewal caused cells to exist in a reduced state, extrinsic factors that induced NSPC differentiation led to a more oxidized intracellular state, suggesting that redox state could be a critical modulator of the cell fate decision between selfrenewal and differentiation [14] In line with these findings, oxidative stress was shown to trigger the progressive loss of the stemness in NSPCs and promote spontaneous neuronal differentiation [15]. Quadrella incana leaf contributed to the maintenance of NSPCs by upregulating glycolytic flux and redox potential

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