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

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

doi:10.1002/stem.1006

Cited by 91 publications

(114 citation statements)

References 72 publications

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“…S6 B-D). This observation that loss of RelA depresses early neurogenesis in the olfactory neuroepithelium in vivo is in keeping with a previous study suggesting that NF-κB signaling is required for initiation of neural stem cell differentiation in vitro (41).…”

Section: Loss Of Rela Decreases Neuronal Differentiation and Increasesupporting

confidence: 92%

Acute inflammation regulates neuroregeneration through the NF-κB pathway in olfactory epithelium

Chen

Reed

Lane

2017

Proc. Natl. Acad. Sci. U.S.A.

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Adult neural stem cells/progenitor cells residing in the basal layer of the olfactory epithelium are capable of reconstituting the neuroepithelium even after severe damage. The molecular events underlying this regenerative capacity remain elusive. Here we show that the repair of neuroepithelium after lesioning is accompanied by an acute, but self-limited, inflammatory process. Attenuation of inflammatory cell recruitment and cytokine production by dexamethasone impairs proliferation of progenitor horizontal basal cells (HBCs) and subsequent neuronal differentiation. Using TNF-α receptor-deficient mice, we identify TNF-α signaling as an important contributor to this inflammatory and reparative process, mainly through TNF-α receptor 1. HBC-selective genetic ablation of RelA (p65), the transcriptional activator of the NF-κB pathway, retards inflammation and impedes proliferation at the early stages of regeneration and suggests HBCs directly participate in cross-talk between immune response and neurogenesis. Loss of RelA in the regenerating neuroepithelium perturbs the homeostasis between proliferation and apoptosis while enhancing JNK signaling. Together, our results support a model in which acute inflammation after injury initiates important regenerative signals in part through NF-κB-mediated signaling that activates neural stem cells to reconstitute the olfactory epithelium.neuroregeneration | inflammation | olfactory stem cells | NF-κB

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Section: Loss Of Rela Decreases Neuronal Differentiation and Increasesupporting

confidence: 92%

Acute inflammation regulates neuroregeneration through the NF-κB pathway in olfactory epithelium

Chen

Reed

Lane

2017

Proc. Natl. Acad. Sci. U.S.A.

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show abstract

“…In agreement with this, C/EBPβ deficient mice show reduced neurogenesis in vitro and in vivo (Cortes-Canteli et al 2011). Therefore, with the exception of one study reporting that C/EBPβ inhibition is associated with TNFα-induced neuronal differentiation of neural stem cells (Zhang et al 2012a), most experimental data support a role for C/EBPβ in promoting neurogenesis. There are in contrast no reports showing a role for C/EBPδ in neurogenesis.…”

Section: Neurogenesismentioning

confidence: 57%

C/EBPβ and C/EBPδ transcription factors: Basic biology and roles in the CNS

Pulido-Salgado

Vidal-Taboada

Saura

2015

Progress in Neurobiology

141

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“…In addition, IKKβ signaling has been shown to be important for stem cell differentiation and hematopoietic cell development (50,51). For example, the canonical IKKβ/NF-κB pathway is required for initial differentiation of neural stem cells (51). Proinflammatory signaling in adipose tissue has been demonstrated to be important for HF-induced adipogenesis and adipose tissue expansion (52).…”

Section: Discussionmentioning

confidence: 99%