神經幹細胞於奈米基材POMA上分化之MicroRNAs表現分析

越來越多的有關奈米基材的研究被應用於生醫組織工程上，尤其如無法再生的神經系統，神經幹細胞(Neural Stem cell)於奈米基材的分化與生長，提供了一個治療相關神經組織受損的希望。poly-(o-methoxyaniline)(POMA)是一個先前被研究的奈米基材，該基材具有促進神經幹細分化之現象，該基材於表觀遺傳學調控(epigenetic)之機制已於先前於陳中庸及金亭佑老師實驗室發展出之PSSH方法完成。為進一步了解神經幹細胞於POMA基材之分化情形，本研究使用微型核糖核酸晶片(MicroRNAs microarrays)於POMA及PDL做為對照之microRNAs表現情形，經由生物資訊的方法，找出神經幹細胞於該基材之MicroRNAs可能的調控機制。最終經由功能及篩選的結果得到16個同時調控於POMA及PDL預測基因，分為為8個有關神經細胞生成(neuritogenesis) (CYTH2, DOCK1, FGFR1, FNBP1, MSN, PACSIN1, SEPT11, RIMS4) 4 個有關增殖(proliferation)(ERBB2, RB1, CPEB1, IGF-1)與4個有關分化(differentiation) (ERBB2, NCAM1, RIMS4, IGF-1) 的預測基因。這些預測基因需要更多實驗進行證實，於microRNAs 等級的分析中，與先前的結果可以發現POMA是一個可被接受之奈米基材。

關鍵字

神經幹細胞分化；微型核醣核酸

並列摘要

The application of nanofibers in tissue engineering offers an option and hope of cellular therapy, especially in the central nervous system. A novel nano substrate poly-(o-methoxyaniline)(POMA) were seeded with neural stem cells and found to have more differential efficiency compared with PDL. The epigenetic mechanism of neural stem cells differentiation on POMA had been analyzed by PSSH before. Hence, to understand its properties, differentially expressed miRNAs targets of neural stem cells on POMA, PDL-coated glass were identified by microRNA microarray. We clustered miRNA target genes via Ingenuity Pathway Analysis (IPA) based on their functions and roles in neural cell differentiation. Sixteen differentially expressed genes were selected with significant role in neural stem cells differentiation in both POMA and PDL: eight (CYTH2, DOCK1, FGFR1, FNBP1, MSN, PACSIN1, SEPT11, RIMS4) in neuritogenesis, four (ERBB2, RB1, CPEB1, IGF-1) in proliferation and four (ERBB2, NCAM1, RIMS4, IGF-1) in differentiation. However, three genes had opposite regulation direction in POMA and PDL, which are L1CAM, NFASC and NTRK2. These predicted genes need further confirmations. In conclusion, POMA fibers could be a candidate as a scaffold for NSC differentiation in miRNAs level.

並列關鍵字

neural stem cell differentiation ； microRNAs

參考文獻

Bao, S., Q. Wu, Z. Li, S. Sathornsumetee, H. Wang, R. E. McLendon, A. B. Hjelmeland and J. N. Rich (2008). "Targeting cancer stem cells through L1CAM suppresses glioma growth." Cancer Res 68(15): 6043-6048.

2. Bartel, D. P. (2004). "MicroRNAs: genomics, biogenesis, mechanism, and function." Cell 116(2): 281-297.

3. Bava, F.-A., C. Eliscovich, P. G. Ferreira, B. Minana, C. Ben-Dov, R. Guigo, J. Valcarcel and R. Mendez (2013). "CPEB1 coordinates alternative 3[prime]-UTR formation with translational regulation." Nature advance online publication.

4. Bueno, M. J., I. Perez de Castro and M. Malumbres (2008). "Control of cell proliferation pathways by microRNAs." Cell Cycle 7(20): 3143-3148.

6. Conaco, C., S. Otto, J. J. Han and G. Mandel (2006). "Reciprocal actions of REST and a microRNA promote neuronal identity." Proc Natl Acad Sci U S A 103(7): 2422-2427.

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神經幹細胞於奈米基材POMA上分化之MicroRNAs表現分析

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