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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

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


Authors

Liyun Chen

Chung-Teng Wang

Nicholas R. Forsyth



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.

Journal Article Type Article
Acceptance Date Jul 13, 2020
Online Publication Date Jul 25, 2020
Publication Date Jul 25, 2020
Publicly Available Date Mar 29, 2024
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

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