Chronic developmental hypoxia alters rat lung immune cell transcriptomes during allergic airway inflammation

It is unknown how hypoxia exposure beginning at conception and maintained through adulthood, chronic developmental hypoxia (CDH), effects immune cell populations in the lung. This study utilized single cell RNA sequencing in a rat model of CDH combined with a model of OVA-induced asthma or a non-allergic model to assess the effect of CDH on lung immune cell populations in the context of allergic airway disease and in a non-allergic state. Overall design: Rat breeding pairs were acclimated to either hypoxic (15% FiO2) (CDH) or normoxic/room air (RA) conditions for 3 weeks. Pups born to the breeding pairs were then weaned and raised in the same conditions in which they were born for. At 4-6 weeks of age, both hypoxic and normoxic animals received IP OVA (250ug in PBS) and pertussis toxin (50ng) followed by a booster 8-12 days later. Both hypoxic and normoxic rats were then challenged with either intranasal OVA or a PBS vehicle control for 3 days. Rats were euthanized, and lungs were digested with 1% Collagenase A and processed into single-cell suspensions prior to sequencing on the 10X Gennomics Chromium platform.