Integrated ATAC-seq and RNA-seq analysis identifies key regulatory elements in NK cells activated with feeder cells...

Area of Science:

• Immunology
• Cell Biology
• Genomics

Background:

• Natural killer (NK) cells are crucial for allogeneic immunotherapy, requiring ex vivo expansion for clinical use.
• Understanding the molecular mechanisms driving NK cell expansion is essential for optimizing immunotherapy treatments.

Purpose of the Study:

• To investigate the transcriptomic and epigenetic changes in NK cells during ex vivo expansion.
• To identify key transcription factors and regulatory elements involved in NK cell activation and proliferation.

Main Methods:

• Comparative analysis of NK cell transcriptomes and chromatin accessibility before and after 7 days of feeder cell and cytokine activation.
• Identification and analysis of transcription factor binding activity and super-enhancer regions.

Main Results:

• Significant differences in gene expression and chromatin accessibility were observed in activated NK cells, particularly near enhancers.
• Differential binding of key transcription factors (AP-1, IRF4, STATs, T-bet, Eomes, bHLHE40) was identified.
• Stable and dynamic super-enhancers were characterized, correlating with transcriptional activity.

Conclusions:

• The study provides a comprehensive transcriptomic and epigenetic landscape of activated NK cells.
• These findings offer insights into the molecular drivers of NK cell expansion, potentially enabling the development of enhanced NK cell therapies.