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Research Paper|Volume 15, Issue 23|pp 14086—14108

Transcriptome research of human amniocytes identifies hub genes associated with developmental dysplasia in down syndrome

Zhenglong Guo1,2, Hai Xiao1,2, Wenke Yang1,2, Tao Li4, Bingtao Hao1,2,3, Shixiu Liao1,2
  • 1Henan 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
  • 2School of Medicine, People’s Hospital of Henan University, Henan University, Zhengzhou, China
  • 3Cancer Research Institute, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China
  • 4Department of Medicine Laboratory, Fuwai Central China Cardiovascular Hospital, Zhengzhou, China
* Equal contribution
Received: June 15, 2023Accepted: November 2, 2023Published: December 12, 2023
https://doi.org/10.18632/aging.205291

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.