Universität zu Köln

Nayernia, Zeynab, Colaianna, Marilena, Robledinos-Anton, Natalia, Gutzwiller, Eveline ORCID: 0000-0002-7537-7545, Sloan-Bena, Frederique, Stathaki, Elisavet, Hibaoui, Yousef, Cuadrado, Antonio, Hescheler, Juergen, Stasia, Marie-Jose, Saric, Tomo, Jaquet, Vincent ORCID: 0000-0003-2229-2406 and Krause, Karl-Heinz ORCID: 0000-0002-9033-6768 (2017). Decreased neural precursor cell pool in NADPH oxidase 2-deficiency: From mouse brain to neural differentiation of patient derived iPSC. Redox Biol., 13. S. 82 - 94. AMSTERDAM: ELSEVIER. ISSN 2213-2317

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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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Nayernia, Zeynab UNSPECIFIED UNSPECIFIED UNSPECIFIED Colaianna, Marilena UNSPECIFIED UNSPECIFIED UNSPECIFIED Robledinos-Anton, Natalia UNSPECIFIED UNSPECIFIED UNSPECIFIED Gutzwiller, Eveline UNSPECIFIED orcid.org/0000-0002-7537-7545 UNSPECIFIED Sloan-Bena, Frederique UNSPECIFIED UNSPECIFIED UNSPECIFIED Stathaki, Elisavet UNSPECIFIED UNSPECIFIED UNSPECIFIED Hibaoui, Yousef UNSPECIFIED UNSPECIFIED UNSPECIFIED Cuadrado, Antonio UNSPECIFIED UNSPECIFIED UNSPECIFIED Hescheler, Juergen UNSPECIFIED UNSPECIFIED UNSPECIFIED Stasia, Marie-Jose UNSPECIFIED UNSPECIFIED UNSPECIFIED Saric, Tomo UNSPECIFIED UNSPECIFIED UNSPECIFIED Jaquet, Vincent UNSPECIFIED orcid.org/0000-0003-2229-2406 UNSPECIFIED Krause, Karl-Heinz UNSPECIFIED orcid.org/0000-0002-9033-6768 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-217083
DOI:	10.1016/j.redox.2017.04.026
Journal or Publication Title:	Redox Biol.
Volume:	13
Page Range:	S. 82 - 94
Date:	2017
Publisher:	ELSEVIER
Place of Publication:	AMSTERDAM
ISSN:	2213-2317
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language STEM-CELLS; SUBVENTRICULAR ZONE; OXIDATIVE-STRESS; HIPPOCAMPAL NEUROGENESIS; ADULT NEUROGENESIS; NMDA RECEPTOR; SELF-RENEWAL; NOX FAMILY; HUMAN ES; NEURONS Multiple languages Biochemistry & Molecular Biology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/21708