PT  - JOURNAL ARTICLE
AU  - Gang Wu
AU  - Yin Yeng Lee
AU  - Evelyn M. Gulla
AU  - Andrew Potter
AU  - Joseph Kitzmiller
AU  - Marc D Ruben
AU  - Nathan Salomonis
AU  - Jeffrey A. Whitsett
AU  - Lauren J Francey
AU  - John B Hogenesch
AU  - David F. Smith
TI  - Short-term exposure to intermittent hypoxia in mice leads to changes in gene expression seen in chronic pulmonary disease
AID  - 10.1101/2020.03.06.981241
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.03.06.981241
4099  - http://biorxiv.org/content/early/2020/03/25/2020.03.06.981241.short
4100  - http://biorxiv.org/content/early/2020/03/25/2020.03.06.981241.full
AB  - Obstructive sleep apnea (OSA) results from intermittent episodes of airway collapse and hypoxia and is associated with a host of health complications including dementia, diabetes, heart failure, and stroke. Cellular mechanisms causing disease progression across multiple systems in OSA are unknown. Although it is known that pulmonary diseases share general mechanisms, such as systemic inflammation and oxidative stress, there is an incomplete understanding of the early-stage changes to the lung from OSA. Using intermittent hypoxia (IH) as a mouse model of OSA, we showed profound cell-type specific changes in genome-wide expression in the lung. With single-cell RNA analysis, we identified substantial similarities between lungs of mice exposed to IH and human lung tissue from patients with pulmonary disease––most notably pulmonary hypertension, COPD, and asthma. Many IH-responsive genes encode targets of drugs currently available to treat pulmonary disease. Present data provide insights into the initiation of specific cellular responses which drive disease progression in a model of OSA. This information can help direct therapies to the most relevant cells and molecular pathways.SIGNIFICANCE STATEMENT We demonstrated profound early cell-type specific changes in genome wide expression in the lung from mice exposed to intermittent hypoxia (IH), a model for obstructive sleep apnea (OSA). Using single-cell RNA analysis, we also identified substantial similarities between the lungs from these mice and human lung tissue from patients with unrelated pulmonary disease. As the first single cell analysis of lung from a murine model of OSA, our data provide insight into the early cellular responses that drive disease progression. By identifying the roles of individual cells in disease, we have the opportunity to test targeted therapeutics, focusing specifically on the most relevant cells and upstream molecular pathways.