Genes and Pathways Underpinning Klinefelter Syndrome at Bulk and Single-Cell Levels.

Publisher: Kluwer Academic/Plenum Publishers Country of Publication: United States NLM ID: 0126611 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1573-4927 (Electronic) Linking ISSN: 00062928 NLM ISO Abbreviation: Biochem Genet Subsets: MEDLINE

Publication: 1999- : New York : Kluwer Academic/Plenum Publishers
Original Publication: New York, Plenum Press.

Klinefelter Syndrome*/genetics ; Single-Cell Analysis*; Humans ; Male ; Transcriptome ; Signal Transduction ; Gene Expression Profiling

Klinefelter syndrome (KS) is the most frequent genetic anomaly in infertile men. Given its unclear mechanism, we aim to investigate critical genes and pathways in the pathogenesis of KS based on three bulk and one single-cell transcriptome data sets from Gene Expression Omnibus. We merged two data sets (GSE42331 and GSE47584) with human KS whole blood samples. When comparing the control and KS samples, five hub genes, including defensin alpha 4 (DEFA4), bactericidal permeability increasing protein (BPI), myeloperoxidase (MPO), intelectin 1 (ITLN1), and Xg Glycoprotein (XG), were identified. Besides, infiltrated degree of certain immune cells such as CD56 ^bright NK cell were positively associated with the expression of ITLN1 and XG. Kyoto Encyclopedia of Genes and Genomes analysis identified upregulated phosphatidylinositol 3-kinase (PI3K)/AKT pathway in KS. Gene set enrichment analysis followed by gene set variation analysis confirmed the upregulation of G2M checkpoint and heme metabolism in KS. Thereafter, the GSE200680 data set was used for external validation of the expression variation of hub genes from healthy to KS testicular samples, and each hub gene yielded excellent discriminatory capability for KS without exception. At the single-cell level, the GSE136353 data set was utilized to evaluate intercellular communication between different cell types in KS patient, and strong correlations were detected between macrophages/ dendritic cells/ NK cells and the other cell types. Collectively, we provided hub genes, pathways, immune cell infiltration degree, and cell-cell communication in KS, warranting novel insights into the pathogenesis of this disease.
Competing Interests: Declarations. Competing interests: All co-authors declared no conflict of interest related to this study. Ethical Approval: The medical research ethics committee of Nanjing Municipal Center for Disease Control and Prevention approved the study design of this work. Consent for Publication: All authors.
(© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

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Keywords: Bulk; Hub gene; KS; Pathway; Single-cell

Date Created: 20240220 Date Completed: 20241128 Latest Revision: 20241128

20241202

10.1007/s10528-024-10689-6

38374521