Exploring the Potential Role of Rosmarinic Acid in Neuronal Differentiation of Human Amnion Epithelial Cells by Microarray Gene Expression Profiling

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.