Astrocyte-derived interleukin-6 promotes specific neuronal differentiation of neural progenitor cells from adult hippocampus.
Astrocyte-derived interleukin-6 promotes specific neuronal differentiation of neural progenitor cells from adult hippocampus.
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DOI：
10.1002/jnr.22447
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发表时间：
2010-10
影响因子：
4.2
通讯作者：
Sakaguchi, Donald S.
中科院分区：
文献类型：
--
作者：
Oh, Jisun;McCloskey, Michael A.;Blong, Christopher C.;Bendickson, Lee;Nilsen-Hamilton, Marit;Sakaguchi, Donald S.
本研究的目的是探讨星形胶质细胞衍生因子影响神经前体细胞分化的能力。我们先前证明，在非接触共培养条件下，存在星形胶质细胞衍生的可溶性因子时，大鼠成年海马祖细胞（AHPCs）对神经元标记物III类β-微管蛋白（TUJ 1）的免疫反应性显著增加。利用全细胞膜片钳技术，我们观察到共培养的AHPCs显示出两种显著的电压门控电导--四乙基铵（TEA）敏感的外向电流和快速瞬时内向电流。共培养AHPC的外向和内向电流密度分别约为单独培养细胞的2.5倍和1.7倍。这些结果表明，星形胶质细胞衍生的可溶性因子诱导AHPCs的神经元承诺。为了进一步研究候选神经源性因子对AHPC分化的活性，我们在存在或不存在纯化的大鼠重组白细胞介素-6（IL-6）的情况下培养AHPCs。我们还通过ELISA和RT-qPCR证实了本研究中使用的星形胶质细胞产生IL-6。当AHPCs与IL-6培养6-7天时，TUJ 1免疫反应阳性AHPCs和TUJ 1免疫反应阳性神经突的平均长度显著增加，与无IL-6培养的细胞相比。此外，IL-6增加了内向电流密度的程度相当，因为没有与星形胶质细胞共培养，在外向电流密度，表观静息电位，或细胞电容没有显着差异。这些结果表明，星形胶质细胞衍生的IL-6可能促进AHPC神经元分化。我们的发现对于理解损伤诱导的神经发生和开发使用神经祖细胞的基于细胞的治疗策略具有重要意义。
The purpose of this study was to investigate the ability of astrocyte-derived factors to influence neural progenitor cell differentiation. We previously demonstrated that rat adult hippocampal progenitor cells (AHPCs) immunoreactive for the neuronal marker, class III β-tubulin (TUJ1) were significantly increased in the presence of astrocyte-derived soluble factors under non-contact co-culture conditions. Using whole cell patch clamp analysis, we observed that the co-cultured AHPCs displayed two prominent voltage-gated conductances - tetraethyl ammonium (TEA)-sensitive outward currents and fast transient inward currents. The outward and inward current densities of the co-cultured AHPCs were approximately 2.5-fold and 1.7-fold greater, respectively, than those of cells cultured alone. These results suggest that astrocyte-derived soluble factors induce neuronal commitment of AHPCs. To further investigate the activity of a candidate neurogenic factor on AHPC differentiation, we cultured AHPCs in the presence or absence of purified rat recombinant interleukin-6 (IL-6). We also confirmed that the astrocytes used in this study produced IL-6 by ELISA and RT-qPCR. When AHPCs were cultured with IL-6 for 6-7 days, the TUJ1-immunoreactive AHPCs and the average length of TUJ1-immunoreactive neurites were significantly increased, compared to the cells cultured without IL-6. Moreover, IL-6 increased the inward current density to a comparable extent as did co-culture with astrocytes, with no significant differences in the outward current density, apparent resting potential, or cell capacitance. These results suggest that astrocyte-derived IL-6 may facilitate AHPC neuronal differentiation. Our findings have important implications for understanding injury-induced neurogenesis and developing cell-based therapeutic strategies using neural progenitors.
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影响因子：
46.9
作者：
Fischer, M;Goldschmitt, J;RoseJohn, S
通讯作者：
RoseJohn, S
影响因子：
4.8
作者：
Kornyei, Z.;Gocza, E.;Madarasz, E.
通讯作者：
Madarasz, E.
DOI：
10.1083/jcb.109.2.663
发表时间：
1989-08
期刊：
The Journal of cell biology
影响因子：
--
作者：
Joshi HC;Cleveland DW
通讯作者：
Cleveland DW
影响因子：
4.2
作者：
FERREIRA, A;CACERES, A
通讯作者：
CACERES, A
影响因子：
16.2
作者：
BARRES, BA;CHUN, LLY;COREY, DP
通讯作者：
COREY, DP