Department of Life Sciences and Medicine, Faculty of Science, Technology and Communication, University of Luxembourg, L-1511 Luxembourg, Luxembourg.
NORLUX Neuro-Oncology Laboratory, Department of Oncology, Luxembourg Institute of Health, L-1526 Luxembourg, Luxembourg.
Cells. 2021 Apr 8;10(4):840. doi: 10.3390/cells10040840.
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.
NF-κB 信号通路在发育和炎症过程中至关重要。我们之前已经表明，NF-κB 的激活诱导星形胶质细胞分化为神经祖细胞（NPC）。在这里，我们提供证据表明，NF-κB 通路在 NPC 分化为星形胶质细胞的过程中也起着基本作用。首先，我们表明 NF-κB 通路对于启动星形胶质细胞分化是必需的，因为早期抑制会诱导 NPC 凋亡并阻碍其分化。其次，我们证明持续的 NF-κB 激活会影响 NPC 衍生的星形胶质细胞分化。肿瘤坏死因子（TNF）处理的 NPC 显示 NF-κB 激活，保持其多能性和增殖特性，持续表达不成熟标志物并抑制星形胶质细胞标志物。第三，我们分析了 NF-κB 激活对主要已知的星形胶质细胞分化途径（如 NOTCH 和 JAK-STAT）的影响。我们的研究结果表明，NF-κB 通路在 NPC 分化为星形胶质细胞过程中起着双重基本作用：它促进星形胶质细胞的特化，但持续激活会阻碍其分化。
