Single-Cell Analysis Identifies Thymic Maturation Delay in Growth-Restricted Neonatal Mice

Area of Science:

• Immunology
• Developmental Biology
• Genetics

Background:

• Fetal growth restriction (FGR) is linked to adult diseases but its impact on the immune system is unclear.
• FGR can cause neonatal defects, increasing risks for heart disease, diabetes, and anxiety later in life.

Purpose of the Study:

• To investigate the effects of FGR on thymus cellularity and T-cell development in a mouse model.
• To understand the long-term immunological consequences of FGR.

Main Methods:

• Utilized a mouse model with placental Igf-2 deletion to induce FGR.
• Employed single-cell RNA sequencing (Drop-Seq) to analyze thymus cell populations at postnatal day 6.
• Compared cellularity and gene expression profiles between FGR and control animals.

Main Results:

• FGR mice exhibited reduced thymus mass and ~70% lower cellularity.
• Single-cell RNA sequencing revealed underrepresentation of specific T-cell subsets and a skew towards immature T-cells in FGR animals.
• The T-cell deficit persisted into adulthood despite catch-up growth.

Conclusions:

• FGR significantly disrupts thymus development and T-cell maturation.
• The observed T-cell deficiency in FGR mice has lasting implications for adult immunity.
• Findings in mice correlate with altered immunity observed in growth-restricted human infants, highlighting the role of the in utero environment.