NF-kappa B and TNF Affect the Astrocytic Differentiation from Neural Stem Cells

Cindy Birck, Aurélien Ginolhac, Maria Angeliki S. Pavlou, Alessandro Michelucci, Paul Heuschling, Luc Grandbarbe

Research output: Contribution to journalArticleResearchpeer-review

1 Citation (Scopus)

Abstract

The NF-κB signaling pathway is crucial during development and inflammatory processes. We have previously shown that NF-κB activation induces dedifferentiation of astrocytes into neural progenitor cells (NPCs). Here, we provide evidence that the NF-κB pathway plays also a fundamental role during the differentiation of NPCs into astrocytes. First, we show that the NF-κB pathway is essential to initiate astrocytic differentiation as its early inhibition induces NPC apoptosis and impedes their differentiation. Second, we demonstrate that persistent NF-κB activation affects NPC-derived astrocyte differentiation. Tumor necrosis factor (TNF)-treated NPCs show NF-κB activation, maintain their multipotential and proliferation properties, display persistent expression of immature markers and inhibit astrocyte markers. Third, we analyze the effect of NF-κB activation on the main known astrocytic differentiation pathways, such as NOTCH and JAK-STAT. Our findings suggest that the NF-κB pathway plays a dual fundamental role during NPC differentiation into astrocytes: it promotes astrocyte specification, but its persistent activation impedes their differentiation.

Original languageEnglish
Article number840
JournalCells
Volume10
Issue number4
DOIs
Publication statusPublished - 8 Apr 2021

Keywords

  • Apoptosis
  • Astrocyte
  • Differentiation
  • NF-κB
  • Neural progenitor cell
  • Tumor necrosis factor

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