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Decreased neural precursor cell pool in NADPH oxidase 2-deficiency: From mouse brain to neural differentiation of patient derived iPSC.

Nayernia, Zeynab
Robledinos-Antón, Natalia
Gutzwiller, Eveline
Sloan-Béna, Frédérique
Stathaki, Elisavet
Cuadrado, Antonio
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Published in Redox Biology. 2017, vol. 13, p. 82-93
Abstract There is emerging evidence for the involvement of reactive oxygen species (ROS) in the regulation of stem cells and cellular differentiation. Absence of the ROS-generating NADPH oxidase NOX2 in chronic granulomatous disease (CGD) patients, predominantly manifests as immune deficiency, but has also been associated with decreased cognition. Here, we investigate the role of NOX enzymes in neuronal homeostasis in adult mouse brain and in neural cells derived from human induced pluripotent stem cells (iPSC). High levels of NOX2 were found in mouse adult neurogenic regions. In NOX2-deficient mice, neurogenic regions showed diminished redox modifications, as well as decrease in neuroprecursor numbers and in expression of genes involved in neural differentiation including NES, BDNF and OTX2. iPSC from healthy subjects and patients with CGD were used to study the role of NOX2 in human in vitro neuronal development. Expression of NOX2 was low in undifferentiated iPSC, upregulated upon neural induction, and disappeared during neuronal differentiation. In human neurospheres, NOX2 protein and ROS generation were polarized within the inner cell layer of rosette structures. NOX2 deficiency in CGD-iPSCs resulted in an abnormal neural induction in vitro, as revealed by a reduced expression of neuroprogenitor markers (NES, BDNF, OTX2, NRSF/REST), and a decreased generation of mature neurons. Vector-mediated NOX2 expression in NOX2-deficient iPSCs rescued neurogenesis. Taken together, our study provides novel evidence for a regulatory role of NOX2 during early stages of neurogenesis in mouse and human.
Keywords AnimalsBrain/cytology/metabolismBrain-Derived Neurotrophic Factor/genetics/metabolismCellsCulturedGranulomatous DiseaseChronic/metabolism/pathologyHumansInduced Pluripotent Stem Cells/cytology/metabolismMiceNADPH Oxidase 2/genetics/metabolismNestin/genetics/metabolismNeural Stem Cells/cytology/metabolismNeurogenesisOtx Transcription Factors/genetics/metabolismReactive Oxygen Species/metabolismRepressor Proteins/genetics/metabolism
PMID: 28575744
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Research group Radicaux libres et cellules souches embryonnaires (60)
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NAYERNIA, Zeynab et al. Decreased neural precursor cell pool in NADPH oxidase 2-deficiency: From mouse brain to neural differentiation of patient derived iPSC. In: Redox Biology, 2017, vol. 13, p. 82-93. doi: 10.1016/j.redox.2017.04.026 https://archive-ouverte.unige.ch/unige:112339

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Deposited on : 2018-12-14

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