Loss of Neuroglobin Expression Alters Cdkn1a/Cdk6-Expression Resulting in Increased Proliferation of Neural Stem Cells

脑红蛋白表达的丧失会改变 Cdkn1a/Cdk6 的表达,从而导致神经干细胞增殖增加

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作者:Evi Luyckx, Wendy Van Leuven, Daniel Andre, Alessandra Quarta, Kristien Reekmans, Erik Fransen, Luc Moens, Thomas Hankeln, Peter Ponsaerts, Sylvia Dewilde

Abstract

In the quest to unravel its functional significance, neuroglobin (Ngb), a brain-specific neuroprotective protein, has recently been proposed as an actor in neurodevelopment. As neural stem cells (NSCs) are fundamental during brain development, the present study aimed at investigating the role of Ngb in the growth and proliferation of NSCs by comparing an Ngb-floxed (Ngbfl-)NSC line, equivalent to the wild-type cellular situation, with an in-house created Ngb knockout (NgbKO-)NSC line. NgbKO-NSCs were characterized by an increased growth and proliferation capacity in vitro, supported by RNA sequencing and western blot results reporting the downregulation of Cdkn1a and the upregulation of Cdk6, both enhancing the cell cycle. Based on additional gene ontology enrichment and pathway analyses, we hypothesize that the loss of Ngb affects multiple cellular signaling pathways with the most important being the Akt-Tp53 axis.

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