Nuclear Factor Kappa B Signaling Initiates Early Differentiation of Neural Stem Cells

Yonggang Zhang; Jianjun Liu; Shaohua Yao; Fang Li; Lin Xin; Mowen Lai; Valerie Bracchi-Ricard; Hong Xu; William Yen; Wentong Meng; Shu Liu; Leiting Yang; Shaffiat Karmally; Jin Liu; Hongyan Zhu; Jennifer Gordon; Kamel Khalili; Shanthi Srinivasan; John R Bethea; Xianming Mo; Wenhui Hu

doi:10.1002/stem.1006

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Nuclear Factor Kappa B Signaling Initiates Early Differentiation of Neural Stem Cells

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Nuclear Factor Kappa B Signaling Initiates Early Differentiation of Neural Stem Cells

Yonggang Zhang, Jianjun Liu, Shaohua Yao, Fang Li, Lin Xin, Mowen Lai, Valerie Bracchi-Ricard, Hong Xu, William Yen, Wentong Meng, …

Stem cells (Dayton, Ohio), Vol.30(3), pp.510-524

2012-03

DOI: https://doi.org/10.1002/stem.1006

PMCID: PMC3707487

PMID: 22134901

Abstract

Cell division

Neural stem cells

Neurogenesis

Glial fibrillary acidic protein

Nuclear factor kappa B

EBPβ

Inflammatory mediators, many of which activate the signaling of nuclear factor kappa B (NFκB), have received increasing attention in the field of neurogenesis. NFκB signaling regulates neurite outgrowth and neural plasticity as well as the proliferation/apoptosis and terminal differentiation of neural stem cells (NSCs). Early neurogenesis from NSCs produces identical progeny through symmetric division and committed daughter cells through asymmetric division. Here, we show that NFκB signaling is required for NSC initial differentiation. The canonical IKKβ/IκBα/ p65 pathway is activated during the initial stages of neural differentiation induced by treatment with TNFα or with- drawal of epidermal growth factor/basic fibroblast growth factor. NSC-specific inhibition of NFκB in transgenic mice causes an accumulation of Nestin + /Sox2 + /glial fibrillary acidic protein + NSCs. Inhibition of NFκB signaling in vitro blocks differentiation and asymmetric division and maintains NSCs in an undifferentiated state. The induction of initial differentiation and asymmetry by NFκB signaling occurs through the inhibition of C/EBPβ expression. Our data reveal a novel function of NFκB signaling in early neurogenesis and provide insight into the molecular mechanisms underlying neurodevelopmental disorders and neurodegenerative diseases.

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Collaboration types: Domestic collaboration; International collaboration
Citation topics: 1 Clinical & Life Sciences; 1.5 Neuroscience; 1.5.767 Neurogenesis
Web Of Science research areas: Biotechnology & Applied Microbiology; Cell & Tissue Engineering; Cell Biology; Hematology; Oncology
ESI research areas: Molecular Biology & Genetics

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Title: Nuclear Factor Kappa B Signaling Initiates Early Differentiation of Neural Stem Cells
Creators: Yonggang Zhang - Laboratory of Stem Cell Biology, State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, People’s Republic of China
Jianjun Liu - Department of Neuroscience, Temple University School of Medicine, Philadelphia, Pennsylvania, USA
Shaohua Yao - Laboratory of Stem Cell Biology, State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, People’s Republic of China
Fang Li - Department of Neuroscience, Temple University School of Medicine, Philadelphia, Pennsylvania, USA
Lin Xin - Laboratory of Stem Cell Biology, State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, People’s Republic of China
Mowen Lai - Laboratory of Stem Cell Biology, State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, People’s Republic of China
Valerie Bracchi-Ricard - The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, Florida, USA
Hong Xu - Laboratory of Stem Cell Biology, State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, People’s Republic of China
William Yen - Department of Neuroscience, Temple University School of Medicine, Philadelphia, Pennsylvania, USA
Wentong Meng - Laboratory of Stem Cell Biology, State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, People’s Republic of China
Shu Liu - Department of Neuroscience, Temple University School of Medicine, Philadelphia, Pennsylvania, USA
Leiting Yang - Department of Neuroscience, Temple University School of Medicine, Philadelphia, Pennsylvania, USA
Shaffiat Karmally - The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, Florida, USA
Jin Liu - Laboratory of Stem Cell Biology, State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, People’s Republic of China
Hongyan Zhu - Laboratory of Stem Cell Biology, State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, People’s Republic of China
Jennifer Gordon - Department of Neuroscience, Temple University School of Medicine, Philadelphia, Pennsylvania, USA
Kamel Khalili - Department of Neuroscience, Temple University School of Medicine, Philadelphia, Pennsylvania, USA
Shanthi Srinivasan - Division of Digestive Diseases, Emory University, Atlanta, Georgia, USA
John R Bethea - The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, Florida, USA
Xianming Mo - Laboratory of Stem Cell Biology, State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, People’s Republic of China
Wenhui Hu - Department of Neuroscience, Temple University School of Medicine, Philadelphia, Pennsylvania, USA
Publication Details: Stem cells (Dayton, Ohio), Vol.30(3), pp.510-524
Grant note: R21 OD011155 || OD / Office of the Director : NIH R01 DK075964 || DK / National Institute of Diabetes and Digestive and Kidney Diseases : NIDDK R21 RR032123 || RR / National Center for Research Resources : NCRR
Academic Unit: Miller School of Medicine; Miami Project to Cure Paralysis; UMMG Dept of Neurological Surgery
Language: English
Resource Type: Journal article
PMID: 22134901
PMCID: PMC3707487
Record Identifier: 991031560656502976