Integrative single-cell chromatin and transcriptome analysis of human plasma cell differentiation

Area of Science:

• Immunology and Molecular Biology
• Cellular Differentiation and Epigenetics

Background:

• Plasma cells (PCs) are terminally differentiated B cells crucial for antibody production.
• Understanding the early epigenetic and transcriptional programs driving PC differentiation remains a challenge.

Purpose of the Study:

• To decipher the spatiotemporal epigenetic and transcriptional programs during early PC differentiation.
• To identify key transcription factors and regulatory elements involved in PC maturation.

Main Methods:

• Combined single-cell RNA sequencing (scRNA-seq) and single-cell Assay for Transposase-Accessible Chromatin with high-throughput sequencing (scATAC-seq).
• Utilized an in vitro PC differentiation model to analyze molecular changes.

Main Results:

• Revealed significant heterogeneity in pre-plasmablastic and plasmablastic stages.
• Identified stage-specific transcription factors, including AP-1 family members (BATF3, FOS, BATF), enriched in differentially accessible chromatin regions.
• Demonstrated that a subset of pre-plasmablasts exhibit epigenetic remodeling and unfolded protein response activation, indicating commitment to PC differentiation.

Conclusions:

• The study provides critical insights into the epigenetic and transcriptional reprogramming events governing early PC differentiation.
• The findings offer a valuable resource for understanding the molecular circuits essential for PC maturation and function.
• Identified key transcriptional nodes and epigenetic remodeling crucial for PC development.