Single-cell transcriptomics in bone marrow delineates CD56^dimGranzymeK⁺ subset as intermediate stage in NK cell...

Area of Science:

• Immunology
• Cell Biology
• Genomics

Background:

• Human natural killer (NK) cells are crucial immune cells found in lymphoid tissues.
• NK cells are classified into subsets like CD56brightCD16+, CD56dimCD16+, and lymphoid tissue-resident (lt)NK cells.
• The functional and developmental relationships between these NK cell subsets remain unclear.

Purpose of the Study:

• To elucidate the developmental and functional relationships between human NK cell subsets.
• To identify potential intermediate stages in NK cell differentiation.
• To investigate the early developmental stages of NK cells in bone marrow.

Main Methods:

• Single-cell RNA sequencing (scRNA-seq) was performed on fresh bone marrow NK cells.
• Oligonucleotide-conjugated antibodies targeting CD56, CXCR6, CD117, and CD34 were used.
• Transcriptome, phenotype, and functional analyses were conducted on cells from bone marrow and blood.

Main Results:

• A novel CD56dimGzmK+ NK cell subset was identified, exhibiting intermediate characteristics.
• This subset shares transcriptomic and phenotypic features with both CD56bright and CD56dimGzmK- NK cells.
• Pseudotime analysis revealed a differentiation trajectory for CD56bright, CD56dimGzmK+, and CD56dimGzmK- cells, with ltNK cells being developmentally distinct.
• No developmental link was found between CD34+ progenitors and NK cells in the bone marrow.

Conclusions:

• Single-cell transcriptomics offers novel insights into human NK cell development and differentiation.
• A previously unrecognized intermediate NK cell subset has been characterized.
• The findings suggest that early NK cell developmental stages may not reside in the bone marrow.