Transcriptional profiling reveals altered biological characteristics of chorionic stem cells from women with gestational diabetes

Chen, Liyun; Wang, Chung-Teng; Forsyth, Nicholas R.; Wu, Pensee

Abstract

Background
Gestational diabetes (GDM) is a common complication of pregnancy. The impact of pregnancy complications on placental function suggests that extraembryonic stem cells in the placenta may also be affected during pregnancy. Neonatal tissue-derived stem cells, with the advantages of their differentiation capacity and non-invasive isolation processes, have been proposed as a promising therapeutic avenue for GDM management through potential cell therapy approaches. However, the influence of GDM on autologous stem cells remains unclear. Thus, studies that provide comprehensive understanding of stem cells isolated from women with GDM are essential to guide future clinical applications.

Methods
Human chorionic membrane-derived stem cells (CMSCs) were isolated from placentas of healthy and GDM pregnancies. Transcriptional profiling was performed by DNA microarray, and differentially regulated genes between GDM- and Healthy-CMSCs were used to analyse molecular functions, differentiation, and pathway enrichment. Altered genes and biological functions were validated via real-time PCR and in vitro assays.

Results
GDM-CMSCs displayed, vs. Healthy-CMSCs, 162 upregulated genes associated with increased migration ability, epithelial development, and growth factor-associated signal transduction while the 269 downregulated genes were strongly linked to angiogenesis and cellular metabolic processes. Notably, significantly reduced expression of detoxification enzymes belonging to the aldehyde dehydrogenase gene families (ALDH1A1/1A2, ALDH2, ALDH3) accounted for downregulation across several metabolic pathways. ALDH activity and inhibitor assays indicated that reduced gene expression of ALDHs affected ALDH enzymatic functions and resulted in oxidative stress dysregulation in GDM-CMSCs.

Conclusion
Our combined transcriptional analysis and in vitro functional characterisation have provided novel insights into fundamental biological differences in GDM- and Healthy-CMSCs. Enhanced mobility of GDM-CMSCs may promote MSC migration toward injured sites; however, impaired cellular metabolic activity may negatively affect any perceived benefit.

Citation

Chen, L., Wang, C., Forsyth, N. R., & Wu, P. (2020). Transcriptional profiling reveals altered biological characteristics of chorionic stem cells from women with gestational diabetes. Stem Cell Research and Therapy, 11, Article 319. https://doi.org/10.1186/s13287-020-01828-y

• Journal Article Type: Article
• Acceptance Date: Jul 13, 2020
• Online Publication Date: Jul 25, 2020
• Publication Date: Jul 25, 2020
• Journal: Stem Cell Research & Therapy
• Print ISSN: 1757-6512
• Publisher: BioMed Central
• Peer Reviewed: Peer Reviewed
• Volume: 11
• Article Number: 319
• DOI: https://doi.org/10.1186/s13287-020-01828-y
• Keywords: Aldehyde dehydrogenase, Chorionic stem cells, Gestational diabetes, Microarray analysis, Migration
• Publisher URL: https://doi.org/10.1186/s13287-020-01828-y