The Study of Alternative Splicing Events in Human Induced Pluripotent Stem Cells From a Down's Syndrome Patient

Yunjie Wang; Zexu Li; Guanheng Yang; Linlin Cai; Fan Yang; Yaqiong Zhang; Yitao Zeng; Qingwen Ma; Fanyi Zeng

doi:10.3389/fcell.2021.661381

The Study of Alternative Splicing Events in Human Induced Pluripotent Stem Cells From a Down's Syndrome Patient

Front Cell Dev Biol. 2021 Sep 30:9:661381. doi: 10.3389/fcell.2021.661381. eCollection 2021.

Authors

Yunjie Wang^{1

2}, Zexu Li^{1

2}, Guanheng Yang^{1

2}, Linlin Cai^{1

2}, Fan Yang^{1

2}, Yaqiong Zhang^{1

2}, Yitao Zeng^{1

2}, Qingwen Ma^{1

2}, Fanyi Zeng^{1

2

3}

Affiliations

¹ Shanghai Institute of Medical Genetics, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai, China.
² National Health Commission Key Laboratory of Embryo Molecular Biology, Shanghai Key Laboratory of Embryo and Reproduction Engineering, Shanghai, China.
³ Department of Histoembryology, Genetics & Development, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Abstract

Down's syndrome (DS) is one of the most commonly known disorders with multiple congenital disabilities. Besides severe cognitive impairment and intellectual disability, individuals with DS also exhibit additional phenotypes of variable penetrance and severity, with one or more comorbid conditions, including Alzheimer's disease, congenital heart disease, or leukemia. Various vital genes and regulatory networks had been studied to reveal the pathogenesis of the disease. Nevertheless, very few studies have examined alternative splicing. Alternative splicing (AS) is a regulatory mechanism of gene expression when making one multi-exon protein-coding gene produce more than one unique mature mRNA. We employed the GeneChip Human Transcriptome Array 2.0 (HTA 2.0) for the global gene analysis with hiPSCs from DS and healthy individuals. Examining differentially expressed genes (DEGs) in these groups and focusing on specific transcripts with AS, 466 up-regulated and 722 down-regulated genes with AS events were identified. These genes were significantly enriched in biological processes, such as cell adhesion, cardiac muscle contraction, and immune response, through gene ontology (GO) analysis of DEGs. Candidate genes, such as FN1 were further explored for potentially playing a key role in DS. This study provides important insights into the potential role that AS plays in DS.

Keywords: Down's syndrome; alternative splicing; differentially expressed genes; gene regulation; iPSCs.