Ferdousi Farhana, Sasaki Kazunori, Uchida Yoshiaki, Ohkohchi Nobuhiro, Zheng Yun-Wen, Isoda Hiroko
Alliance for Research on the Mediterranean and North Africa, University of Tsukuba, Tsukuba, Japan.
National Institute of Advanced Industrial Science and Technology, Tsukuba, Japan.
Front Neurosci. 2019 Jul 24;13:779. doi: 10.3389/fnins.2019.00779. eCollection 2019.
In the present study, we conducted microarray gene expression profiling to explore the direction of differentiation of human amnion epithelial cells (hAECs) treated with rosmarinic acid (RA). hAECs have several clinical advantages over other types of stem cells, including availability, low immunogenicity, low rejection rate, non-tumorigenicity, and less ethical constraint. On the other hand, RA is a phenolic compound having several health benefits, including neuroprotective and antidepressant-like activities. In this study, hAECs were isolated from discarded term placenta and were treated with 20 μM RA for 7 days. Microarray gene expression profiling was conducted for three biological replicates of RA-treated and untreated control cells on day 0 and day 7. Gene set enrichment analysis, and gene annotation and pathway analysis were conducted using online data mining tools GSEA and DAVID. Gene expression profiling showed that RA treatment biased hAECs toward ectodermal lineage progression, regulated transcription factors involved in neuronal differentiation, regulated neural specific epigenetic modifiers and several extracellular signaling pathways of neural induction, and significantly inhibited Notch signaling pathway. Gene expression profiling of RA-treated hAECs reveals for the first time a potential role of RA in neural induction and neuronal differentiation of hAECs. Having a naturally occurring compound as differentiation inducer as well as a readily available source of stem cells would have great advantages for the cell-based therapies. Findings from our genome-wide analysis could provide a foundation for further in-depth investigation.
在本研究中,我们进行了基因芯片基因表达谱分析,以探究经迷迭香酸(RA)处理的人羊膜上皮细胞(hAECs)的分化方向。与其他类型的干细胞相比,hAECs具有若干临床优势,包括易于获取、低免疫原性、低排斥率、无致瘤性以及较少的伦理限制。另一方面,RA是一种具有多种健康益处的酚类化合物,包括神经保护和抗抑郁样活性。在本研究中,从废弃的足月胎盘中分离出hAECs,并用20μM RA处理7天。在第0天和第7天,对经RA处理和未处理的对照细胞的三个生物学重复样本进行基因芯片基因表达谱分析。使用在线数据挖掘工具GSEA和DAVID进行基因集富集分析、基因注释和通路分析。基因表达谱分析表明,RA处理使hAECs倾向于外胚层谱系进展,调节参与神经元分化的转录因子,调节神经特异性表观遗传修饰因子以及神经诱导的几个细胞外信号通路,并显著抑制Notch信号通路。经RA处理的hAECs的基因表达谱首次揭示了RA在hAECs的神经诱导和神经元分化中的潜在作用。拥有天然存在的化合物作为分化诱导剂以及易于获得的干细胞来源对于基于细胞的疗法将具有巨大优势。我们全基因组分析的结果可为进一步深入研究提供基础。