Abstract
SummaryNatural killer (NK) cells are innate cytotoxic lymphoid cells (ILCs) involved in the killing of infected and tumor cells. Among human and mouse NK cells from the spleen and blood, we previously identified by single-cell RNA sequencing (scRNAseq) two similar major subsets, NK1 and NK2. Using the same technology, we report here the identification, by single-cell RNA sequencing (scRNAseq), of three NK cell subpopulations in human bone marrow. Pseudotime analysis identified a subset of resident CD56bright NK cells, NK0 cells, as the precursor of both circulating CD56dim NK1-like NK cells and CD56bright NK2-like NK cells in human bone marrow and spleen under physiological conditions. Transcriptomic profiles of bone marrow NK cells from patients with acute myeloid leukemia (AML) exhibited stress-induced repression of NK cell effector functions, highlighting the profound impact of this disease on NK cell heterogeneity. Bone marrow NK cells from AML patients exhibited reduced levels of CD160, but the CD160high group had a significantly higher survival rate.
Highlights
Natural killer (NK) cells are large granular lymphocytes in the innate cytotoxic lymphoid cells (ILCs) family
High-throughput scRNAseq identifies adaptive NK cells in human bone marrow We investigated the heterogeneity of human bone marrow NK
We analyzed ~24,000 flow cytometry-sorted NK cells, defined by their SSC/FSC profile and as CD3− CD14− CD19− CD45+ CD56+ cells, Single-cell profiling reveals the trajectories of natural killer cell
Summary
Natural killer (NK) cells are large granular lymphocytes in the ILC family. NK cells are endowed with the capacity to kill stressed cells, such as infected cells and tumor cells, without specific prior activation, in humans and mice.[1]. Inhibitory receptors are essential for sensing decreases in or total absence of constitutively expressed self MHC-I molecules on target cells. Decreases in MHC-I expression reduce the strength of the inhibitory signals delivered to NK cells, rendering these cells more prone to activation.[2,3] NK cell activation results from the engagement of activating receptors, such as the activating isoforms of Ly49 and KIRs, natural cytotoxicity receptors (NCRs), SLAM (signaling lymphocyte activating molecule)-related receptors, NKG2D and CD16, which can induce NK cell activation by initiating different signaling pathways.[4] The NCR family is composed of three molecules: NKp30 (NCR3, CD337) and NKp44 (NCR2, CD336), which are expressed in humans, and NKp46 (NCR1, CD335), which is expressed in all mammals and is highly conserved between humans and mice. NKp46 is expressed mostly by NK cells and ILC1 cells but is present on a small population of
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
