Bone marrow-derived stromal cells can express neuronal markers by DHA/GPR40 signaling.
Bone marrow-derived stromal cells can express neuronal markers by DHA/GPR40 signaling.
复制标题
DOI：
--
复制
发表时间：
2010-06
影响因子：
5.5
通讯作者：
D. B. Kaplamadzhiev;H. Hisha;Y. Adachi;S. Ikehara;A. Tonchev;N. Boneva;I. V. Pyko;M. Kikuchi;
中科院分区：
文献类型：
--
作者：
D. B. Kaplamadzhiev;H. Hisha;Y. Adachi;S. Ikehara;A. Tonchev;N. Boneva;I. V. Pyko;M. Kikuchi;
神经干细胞在成体神经发生龛中的确切起源仍不清楚。然而，我们之前的研究表明，骨髓细胞是海马新生神经元的潜在祖细胞，多不饱和脂肪酸是G蛋白偶联受体40 （GPR40）信号传导的配体。在这里，我们旨在研究二十二碳六烯酸（DHA）处理的骨髓源性基质细胞（BMSC）是否能在体外表达神经元标记物。我们重点研究了DHA/GPR40信号通路对幼年猕猴克隆扩增BMSC中神经标志物表达的影响。细胞周期分析显示，DHA + bFGF处理诱导BMSC增殖减少，G0静息期细胞增多。利用RT-PCR、Western blot和免疫细胞化学检测巢蛋白阳性祖细胞通过未成熟神经元（β iii -微管蛋白阳性）到成熟神经元（NF-M和map2阳性）表型的转变。与未处理的BMSC相比，我们检测到bFGF诱导后GPR40 mRNA和蛋白表达显著增加。GPR40配体的代表DHA的加入导致GPR40显著下调，即G蛋白偶联受体特异性内化，随后神经元标记物如β iii -微管蛋白、NF-M和Map2上调。这些数据表明，成年灵长类动物BMSC可以在DHA/GPR40信号的帮助下表达神经元标记物。
The exact origin of neural stem cells in the adult neurogenesis niche remains unknown. Our previous studies, however, indicated an implication of both bone marrow cells as potential progenitors of hippocampal newborn neurons and polyunsaturated fatty acids as ligands of G protein-coupled receptor 40 (GPR40) signaling. Here, we aimed at studying whether bone marrow-derived stromal cells (BMSC) treated by docosahexaenoic acid (DHA) can express neuronal markers in vitro. We focused on implication of DHA/GPR40 signaling for the expression of neural markers in clonally-expanded BMSC from young macaque monkeys. Cell cycle analysis revealed that the DHA plus bFGF treatment induced a decrease of BMSC proliferation and increased the cells in the G0 resting phase. The transitions from nestin-positive progenitors via immature neuronal (beta III-tubulin-positive) to mature neuronal (NF-M and Map2-positive) phenotypes were examined using RT-PCR, Western blot and immunocytochemistry. We detected a significant increase of GPR40 mRNA and protein expression after bFGF induction, being compared with the untreated BMSC. Addition of DHA, a representative GPR40 ligand, led to a significant down-regulation of GPR40, i.e., G protein-coupled receptor-specific internalization, with a subsequent upregulation of neuronal markers such as beta III-tubulin, NF-M and Map2. These data altogether suggest that adult primate BMSC can express neuronal markers with the aid of DHA/GPR40 signaling.