Research Paper Volume 15, Issue 23 pp 14086—14108
Transcriptome research of human amniocytes identifies hub genes associated with developmental dysplasia in down syndrome
- 1 Henan Provincial Key Laboratory of Genetic Diseases and Functional Genomics, National Health Commission Key Laboratory of Birth Defects Prevention, Medical Genetic Institute of Henan Province, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, Zhengzhou, China
- 2 School of Medicine, People’s Hospital of Henan University, Henan University, Zhengzhou, China
- 3 Cancer Research Institute, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China
- 4 Department of Medicine Laboratory, Fuwai Central China Cardiovascular Hospital, Zhengzhou, China
Received: June 15, 2023 Accepted: November 2, 2023 Published: December 12, 2023
https://doi.org/10.18632/aging.205291How to Cite
Copyright: © 2023 Guo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Trisomy 21, or Down syndrome (DS), is the most frequent human autosomal chromosome aneuploidy, which leads to multiple developmental disorders, especially mental retardation in individuals. The presence of an additional human chromosome 21 (HSA21) could account for the pathological manifestations in DS. In this study, we analyzed the mRNA gene expression profile of DS-derived amniocytes compared with normal amniocytes, aiming to evaluate the relationship between candidate dysregulated HSA21 genes and DS developmental phenotypes. Differentially expressed genes (DEGs) included 1794 upregulated genes and 1411 downregulated genes, which are mainly involved in cell adhesion, inflammation, cell proliferation and thus may play an important role in inducing multiple dysplasia during DS fetal development. Furthermore, STRING protein network studies demonstrated 7 candidate HSA21 genes participated Gene Ontology (GO) terms: cell adhesion and extracellular matrix remodeling (COL6A1, COL6A2, COL18A1, ADAMTS5, JAM2, and POFUT2), inflammation and virus infection response (MX1 and MX2), histone modification and chromatin remodeling (NRIP1), glycerolipid and glycerophospholipid metabolism (AGPAT3), mitochondrial function (ATP5PF and ATP5PO), synaptic vesicle endocytosis (ITSN1 and SYNJ1) and amyloid metabolism (APP). Meanwhile, GSEA enrichment identified several transcription factors and miRNAs, which may target gene expression in the DS group. Our study established connections between dysregulated genes, especially HSA21 genes, and DS-associated phenotypes. The alteration of multiple pathways and biological processes may contribute to DS developmental disorders, providing potential pathogenesis and therapeutic targets for DS.