Thesis
Single-Cell Transcriptomics Unravels Natural Killer Cell Heterogeneity Across Subcutaneous Adipose Tissue, Epididymal Adipose Tissue, and Spleen in Lean and Obese Mice
The crosstalk between natural killer (NK) cells and adipose tissue has gained significant interest due to
its critical role in shaping the adipose tissue microenvironment and influencing metabolic homeostasis.
It is now widely acknowledged that the activation of NK cells and macrophages in visceral adipose
tissue (VAT) during obesity strongly contributes to insulin resistance. However, current insights into
NK cell diversity in different adipose tissue types, and mechanisms behind their selective activation in
VAT during the progression of obesity still remains poorly understood. Utilizing single-cell RNA
sequencing (scRNA-seq), this study profiled mice NK cell diversity isolated from subcutaneous adipose
tissue (SAT), epididymal adipose tissue, as well as the spleen in both lean and obese conditions. This
study revealed multiple NK cell clusters across adipose tissues and spleen, including four major splenic
NK cell clusters, four major adipose tissue NK cell clusters, one proliferating NK cell cluster, and two
minor NK cell clusters. Notably, this study also identified three clusters resembling type I innate
lymphoid cells (ILC1s), while two clusters remaining uncharacterized. Cell clustering and markers
analyses revealed tissue-specific transcriptional programs of each NK cell and ILC1 cluster. Collectively,
this study provided a general understanding of NK cells and ILC1s heterogeneity in adipose tissues and
spleen.
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