NFAT Transcription Factors Regulate Survival, Proliferation, Migration, and Differentiation of Neural Precursor Cells
NFAT Transcription Factors Regulate Survival, Proliferation, Migration, and Differentiation of Neural Precursor Cells
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DOI：
10.1002/glia.22797
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发表时间：
2015-06-01
期刊：
影响因子：
6.2
通讯作者：
Tranque, Pedro
中科院分区：
文献类型：
--
作者：
Serrano-Perez, Maria C.;Fernandez, Miriam;Tranque, Pedro
研究调节神经前体细胞（NPC）存活、增殖和分化的因素对于理解神经发育和脑再生至关重要。活化T细胞核因子（NFAT）是一个转录因子家族，除了在发育过程中发挥关键作用外，还可以影响这些过程，例如刺激神经元中的轴突生长，免疫系统细胞的成熟，心脏瓣膜形成以及骨骼肌和骨骼的分化。有趣的是，NFAT信号也可以促进成人细胞分化，参与组织再生。本研究的目的是评估NFAT亚型在NPC中的表达，并研究其在NPC存活、增殖、迁移和分化中的可能作用。我们的研究结果表明，NFAT蛋白不仅在海马和脑室下区（SVZ）等神经源性脑区有活性，而且在培养的NPC中也有活性。用肽VIVIT抑制NFAT活化通过减少增殖和增加细胞死亡来减少NPC培养物中的神经球大小和细胞密度。VIVIT还减少了NPC的迁移以及NPC中星形胶质细胞和神经元的分化。此外，我们确定NFATc3作为NPC培养物中的主要NFAT同种型，发现通过腺病毒感染表达的NFATc3的组成型活性形式减少NPC增殖，刺激迁移，并且是NPC分化为星形胶质细胞和神经元的有效诱导剂。总之，我们的工作揭示了NFAT信号在NPC存活、增殖和分化中的积极作用，并突出了其在组织再生中的治疗潜力。GLIA 2015; 63：987 - 1004
The study of factors that regulate the survival, proliferation, and differentiation of neural precursor cells (NPCs) is essential to understand neural development as well as brain regeneration. The Nuclear Factor of Activated T Cells (NFAT) is a family of transcription factors that can affect these processes besides playing key roles during development, such as stimulating axonal growth in neurons, maturation of immune system cells, heart valve formation, and differentiation of skeletal muscle and bone. Interestingly, NFAT signaling can also promote cell differentiation in adults, participating in tissue regeneration. The goal of the present study is to evaluate the expression of NFAT isoforms in NPCs, and to investigate its possible role in NPC survival, proliferation, migration, and differentiation. Our findings indicate that NFAT proteins are active not only in neurogenic brain regions such as hippocampus and subventricular zone (SVZ), but also in cultured NPCs. The inhibition of NFAT activation with the peptide VIVIT reduced neurosphere size and cell density in NPC cultures by decreasing proliferation and increasing cell death. VIVIT also decreased NPC migration and differentiation of astrocytes and neurons from NPCs. In addition, we identified NFATc3 as a predominant NFAT isoform in NPC cultures, finding that a constitutively-active form of NFATc3 expressed by adenoviral infection reduces NPC proliferation, stimulates migration, and is a potent inducer of NPC differentiation into astrocytes and neurons. In summary, our work uncovers active roles for NFAT signaling in NPC survival, proliferation and differentiation, and highlights its therapeutic potential for tissue regeneration. GLIA 2015;63:987-1004