Cell-Cell Connection Enhances Proliferation and Neuronal Differentiation of Rat Embryonic Neural Stem/Progenitor Cells.

Cell-Cell Connection Enhances Proliferation and Neuronal Differentiation of Rat Embryonic Neural Stem/Progenitor Cells.
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细胞间连接增强大鼠胚胎神经干/祖细胞的增殖和神经元分化

DOI:
10.3389/fncel.2017.00200
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发表时间:
2017
影响因子:
5.3
通讯作者:
Liu Y
Liu Y
中科院分区:
医学2区
文献类型:
--
作者:
Jiao Q;Li X;An J;Zhang Z;Chen X;Tan J;Zhang P;Lu H;Liu Y

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细胞间相互作用作为一种生态位信号,在干细胞静止与增殖或分化的平衡中起着重要作用。为了探讨细胞间连接对神经干/祖细胞(NSCs/NPC)增殖和分化的影响及其可能机制,在传代时,将NSCs/NPC按常规解离成单个细胞(命名为组I)或机械研磨成单个细胞和含有直接细胞间连接的小细胞簇的混合物(命名为组II)。观察NSCs/NPCs的增殖、分化等生物学行为。并比较细胞间隙连接通道、神经营养因子的表达及MAPK信号的磷酸化状态,探讨其可能的作用机制。结果表明,与I组相比,II组的NSCs/NPCs存活良好,并具有更好的神经元分化。与此相一致的是,连接蛋白45(Cx45)以及脑源性神经营养因子(BDNF)和神经营养因子3(NT-3)在II组中的表达显著高于I组。Ⅱ组ERK 1/2和JNK 2磷酸化水平也显著上调,而p38磷酸化水平无明显变化。抑制ERK和JNK磷酸化后,I组和II组NSCs/NPCs生物学行为的差异完全消失。这些结果表明,第II组中的细胞-细胞连接通过上调间隙连接和神经营养因子的表达来增强NSCs/NPCs的存活、增殖和神经元分化。MAPK信号- ERK和JNK可能参与了这种增强。维持直接的细胞-细胞连接的努力是值得的,以提供更有利的生态位为NSC/NPCs的生存,增殖和神经元分化。
Cell-cell interaction as one of the niche signals plays an important role in the balance of stem cell quiescence and proliferation or differentiation. In order to address the effect and the possible mechanisms of cell-cell connection on neural stem/progenitor cells (NSCs/NPCs) proliferation and differentiation, upon passaging, NSCs/NPCs were either dissociated into single cell as usual (named Group I) or mechanically triturated into a mixture of single cell and small cell clusters containing direct cell-cell connections (named Group II). Then the biological behaviors including proliferation and differentiation of NSCs/NPCs were observed. Moreover, the expression of gap junction channel, neurotrophic factors and the phosphorylation status of MAPK signals were compared to investigate the possible mechanisms. Our results showed that, in comparison to the counterparts in Group I, NSCs/NPCs in Group II survived well with preferable neuronal differentiation. In coincidence with this, the expression of connexin 45 (Cx45), as well as brain derived neurotrophic factor (BDNF) and neurotrophin 3 (NT-3) in Group II were significantly higher than those in Group I. Phosphorylation of ERK1/2 and JNK2 were significantly upregulated in Group II too, while no change was found about p38. Furthermore, the differences of NSCs/NPCs biological behaviors between Group I and II completely disappeared when ERK and JNK phosphorylation were inhibited. These results indicated that cell-cell connection in Group II enhanced NSCs/NPCs survival, proliferation and neuronal differentiation through upregulating the expression of gap junction and neurotrophic factors. MAPK signals- ERK and JNK might contribute to the enhancement. Efforts for maintaining the direct cell-cell connection are worth making to provide more favorable niches for NSCs/NPCs survival, proliferation and neuronal differentiation.
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