Innate lymphoid cells (ILCs) are increasingly appreciated as important participants in homeostasis and inflammation. Substantial plasticity and heterogeneity among ILC populations have been reported. Here we have delineated the heterogeneity of human ILCs through single-cell RNA sequencing of several hundreds of individual tonsil CD127(+) ILCs and natural killer (NK) cells. Unbiased transcriptional clustering revealed four distinct populations, corresponding to ILC1 cells, ILC2 cells, ILC3 cells and NK cells, with their respective transcriptomes recapitulating known as well as unknown transcriptional profiles. The single-cell resolution additionally divulged three transcriptionally and functionally diverse subpopulations of ILC3 cells. Our systematic comparison of single-cell transcriptional variation within and between ILC populations provides new insight into ILC biology during homeostasis, with additional implications for dysregulation of the immune system.

The etiology of upper airway collapsibility in patients with snoring and obstructive sleep apnea (OSA) remains unclear. Local muscular abnormalities, including neurogenic lesions, could be a contributory factor. The aim of this study was to histologically evaluate the hypothesis of a progressive snorers disease. Biopsies of palatopharyngeal muscle were obtained from 21 patients with habitual snoring and different degrees of upper airway obstruction (10 patients with OSA) and 10 nonsnoring control subjects. Morphological abnormalities, including neurogenic signs (e.g., type grouping), were blindly quantified. The degree of abnormality was significantly increased in patients compared with control subjects. The individual score of abnormalities was significantly correlated to the percentage periodic obstructive breathing but not to oxygen desaturation index. Analyses of the individual fiber-size spectra demonstrated a significantly increased number of hypertrophied and/or atrophied fibers in patients compared with controls. The subjects were also divided into three groups according to their type of nocturnal breathing, i.e., nonsnorers, patients with < 20%, and patients with > or = 45% obstructive breathing. These groups correlated significantly with the degree of abnormality and pathological fiber-size spectra. In conclusion, these results support the hypothesis of a progressive local neurogenic lesion, caused by the trauma of snoring, as a possible contributory factor to upper airway collapsibility.

Natural killer (NK) cells are cytotoxic lymphocytes and play a vital role in controlling viral infections and cancer. In contrast to B and T lymphopoiesis where cellular and regulatory pathways have been extensively characterized, the cellular stages of early human NK cell commitment remain poorly understood. Here we demonstrate that a Lin(-)CD34(+)CD38(+)CD123(-)CD45RA(+)CD7(+)CD10(+)CD127(-) population represents a NK lineage-restricted progenitor (NKP) in fetal development, umbilical cord blood, and adult tissues. The newly identified NKP has robust NK cell potential both in vitro and in vivo, generates functionally cytotoxic NK cells, and lacks the ability to produce T cells, B cells, myeloid cells, and innate lymphoid-like cells (ILCs). Our findings identify an early step to human NK cell commitment and provide new insights into the human hematopoietic hierarchy.