TY - JOUR
T1 - NF-kappa B and TNF Affect the Astrocytic Differentiation from Neural Stem Cells
AU - Birck, Cindy
AU - Ginolhac, Aurélien
AU - Pavlou, Maria Angeliki S.
AU - Michelucci, Alessandro
AU - Heuschling, Paul
AU - Grandbarbe, Luc
N1 - Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/4/8
Y1 - 2021/4/8
N2 - 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.
AB - 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.
KW - Apoptosis
KW - Astrocyte
KW - Differentiation
KW - NF-κB
KW - Neural progenitor cell
KW - Tumor necrosis factor
UR - http://www.scopus.com/inward/record.url?scp=85105148647&partnerID=8YFLogxK
UR - https://www.ncbi.nlm.nih.gov/pubmed/33917855
U2 - 10.3390/cells10040840
DO - 10.3390/cells10040840
M3 - Article
C2 - 33917855
AN - SCOPUS:85105148647
SN - 2073-4409
VL - 10
JO - Cells
JF - Cells
IS - 4
M1 - 840
ER -