# JAG2: A Potential Biomarker for Microtia Identified by Integrated RNA Transcriptome Analysis

## TL;DR

This study identifies JAG2 as a potential biomarker for microtia, a birth defect, using RNA analysis to better understand its causes and improve diagnosis.

## Contribution

The study introduces JAG2 as a novel biomarker for microtia and links it to chondrocyte development via the Notch signaling pathway.

## Key findings

- JAG2 is significantly upregulated in microtia cartilage.
- JAG2 is implicated in chondrocyte maturation and differentiation through the Notch signaling pathway.
- Integration of bulk RNA and single-cell data validated JAG2 as a key gene in microtia pathogenesis.

## Abstract

Microtia, a prevalent congenital maxillofacial deformity, significantly impacts the physical and psychological health of children. Its etiology, especially in non-syndromic cases, remains a complex and partially understood domain, complicating etiological treatment. Recent studies pointed to a genetic predisposition in non-syndromic microtia, yet research on susceptible or pathogenic genes is limited.

This study focused on identifying key biomarker genes in microtia cartilage to elucidate pathogenesis and assist in prenatal diagnosis.

We first collated two bulk transcriptome datasets from the GEO database, followed by functional enrichment analysis and Weighted Gene Co-expression Network Analysis (WGCNA) to pinpoint differentially expressed genes (DEGs) and gene modules. The subsequent intersection of DEGs with WGCNA modules, aided by support vector machine-recursive feature elimination (SVM-RFE) and protein-protein interaction (PPI) networks, predicted potential susceptibility genes for microtia. Finally, we integrated bulk RNA sequencing with single-cell data via the “scissor” R package and further validated it with Real-time PCR and immunofluorescence.

We identified JAG2 as a prominent biomarker for microtia, evidenced by its significant upregulation in microtia cartilage.

Our findings implicate JAG2 in microtia development and suggest its role in chondrocyte maturation and differentiation through Notch signaling pathway activation, shedding light on the potential pathogenesis of microtia.