NF-kappaB and TNF affect the astrocytic differentiation from neural stem cells.

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