Key Genes Associated With Functional Specialization of Neonatal Peripheral Monocytes.

Area of Science:

• Immunology
• Genomics
• Neonatal Medicine

Background:

• Neonatal immune responses differ significantly from adults.
• Severe Group B Streptococcus (GBS) infection poses a major threat to neonates.
• Understanding monocyte functional differences is crucial for neonatal GBS pathogenesis.

Purpose of the Study:

• To identify genes and transcription factors responsible for functional disparities in neonatal versus adult peripheral blood monocytes.
• To elucidate the mechanisms behind severe GBS infection susceptibility in neonates.

Main Methods:

• RNA sequencing (RNA-seq) to detect differentially expressed genes (DEGs) in neonatal and adult monocytes.
• Assay for transposase-accessible chromatin sequencing (ATAC-seq) to identify differentially accessible regions (DARs).
• Integrated RNA-seq and ATAC-seq analyses, validated by quantitative reverse transcription polymerase chain reaction (qRT-PCR).

Main Results:

• Identified 669 overexpressed and 440 underexpressed genes in neonatal monocytes, enriched in bacterial response and cytokine production pathways, respectively.
• Discovered 36,782 differential chromatin accessibility peaks in neonatal monocytes.
• Pinpointed 30 overlapping genes, including validated differential expression of CEBPB, JUN, BATF, PTK2B, ITGAV, ADA2, and RORA.

Conclusions:

• Significant differences exist in the transcriptome and chromatin accessibility of neonatal and adult peripheral monocytes.
• Identified potential genes contributing to neonates' vulnerability to GBS infection.
• Findings enhance understanding of neonatal immune dysfunction in GBS disease and suggest therapeutic targets.