Single-cell-RNA sequencing of bone marrow from mice exposed to chronic intermittent hypoxia

Obstructive sleep apnea, characterized by interrupted breathing during sleep, has been associated with increased cancer risks and mortality at moderate to severe levels. While chronic intermittent hypoxia, a feature of obstructive sleep apnea has been associated with aggressive solid tumors, its effects on blood cancers has been understudied. An important factor in antitumor immune response is the expression of CD3+ and CD8+ T-cells. However, chronic intermittent hypoxia decreases the percent of CD3+ T-cells and obstructive sleep apnea decreases the percent of perforin positive CD8+ T-cells. Over the last decade, cancer immunotherapies have targeted inhibitory receptors such as LAG3 and PD1 to increase the percent of CD8+ cells in solid tumors. Meanwhile, CD3+ cells have been targeted in the bone marrow for treatment in blood cancers.

Therefore, we hypothesized that there will be one distinct population of T-cells which will differentially express LAG3 and PD1 in the bone marrow of mice exposed to chronic intermittent hypoxia. We conducted single cell RNA sequencing on bone marrow cells collected from mice exposed to either chronic intermittent hypoxia or normal oxygen levels. Using advanced genomic tools, we identified three distinct T-cell clusters based on CD3 and CD8 markers. Notably, we identified a CD3-CD8+ cluster as dendritic cells, along with a CD3+CD8+ and CD3+CD8- clusters representing T-cells and natural killer cells. Additionally, we observed differential upregulation of the long non-coding RNA Gm10076 across these populations. These findings underscore the potential role of long noncoding RNAs in chronic intermittent hypoxia. Understanding these molecular mechanisms could lead to novel therapeutic strategies for cancers associated with sleep-disordered breathing conditions.