Single-cell transcriptomics identifies regulatory T cell heterogeneity in gestational diabetes mellitus

Area of Science:

• Immunology
• Reproductive biology
• Genomics

Background:

• Gestational diabetes mellitus (GDM) is a common pregnancy complication linked to hyperglycemia and inflammation.
• Regulatory T cells (Tregs) play a role in immune suppression and are implicated in GDM pathogenesis.
• Transcriptional dysregulation in specific Treg subsets in GDM remains poorly understood.

Purpose of the Study:

• To investigate transcriptional variations in regulatory T cell (Treg) subsets within gestational diabetes mellitus (GDM).
• To identify potential transcriptional markers associated with GDM status.

Main Methods:

• Single-cell RNA sequencing was performed on Tregs and CD4+ T cells from healthy pregnant women and GDM patients.
• Mass cytometry was used to validate findings regarding T cell subsets.

Main Results:

• No significant differences in Treg cluster proportions were observed between healthy and GDM groups.
• Memory CD4+ T cells were more abundant in GDM patients.
• Altered Treg subsets in GDM included naive Tregs with reduced AP-1 expression and effector Tregs with increased angiogenesis gene signaling.
• Gene expression changes in GDM Tregs accurately predicted GDM status in independent cohorts.
• TXNIP, a glucose-regulating gene, was the most significant GDM discriminator in bulk mRNA.

Conclusions:

• This study reveals distinct transcriptional profiles of Treg subsets in GDM patients.
• Identified transcriptional markers hold potential for informing GDM status.