Methods for Isolating and Defining Single-Cell Transcriptomes of Tissue-Resident Human NK Cells

Area of Science:

• Immunology
• Cell Biology

Background:

• Natural killer (NK) cells are crucial innate immune cells involved in tumor surveillance and combating microbial infections.
• Human NK cells exhibit significant heterogeneity, with their phenotype and function influenced by their site of development and residence.
• Current understanding of human NK cells is largely based on blood and bone marrow populations, leaving a knowledge gap regarding tissue-resident NK cells.

Purpose of the Study:

• To address the knowledge gap concerning the development, homing, and function of tissue-resident NK cells.
• To define the transcriptomic profiles and transcriptional regulation of tissue-resident NK cells.
• To establish robust methods for isolating and analyzing tissue-resident NK cells at the single-cell level.

Main Methods:

• Development of methods for the isolation of viable and non-activated tissue-resident NK cells from complex tissues.
• Application of single-cell RNA sequencing (scRNA-seq) for high-resolution transcriptomic analysis.
• Utilizing scRNA-seq to analyze cellular heterogeneity and cell-cell interactions within the tissue microenvironment.

Main Results:

• Successful isolation and transcriptomic profiling of individual NK cells from various tissues.
• Identification of distinct subpopulations of tissue-resident NK cells based on their unique transcriptomic signatures.
• Characterization of NK cell heterogeneity within the tissue microenvironment.

Conclusions:

• The developed methods enable efficient isolation and transcriptomic analysis of tissue-resident NK cells.
• Single-cell RNA sequencing provides unprecedented resolution for understanding NK cell heterogeneity and function in tissues.
• These findings are critical for advancing organ-specific therapies and understanding immune responses in different tissues.