Prematurity alters the progenitor cell program of the upper respiratory tract of neonates

The impact of prematurity in human development and neonatal diseases, such as bronchopulmonary dysplasia, have been widely reported. However, little is known about the effects of prematurity on the programs of stem cell self-renewal and differentiation of the upper respiratory epithelium, key for adaptation to neonatal life. Here we developed a minimally invasive methodology for isolation and functional analysis of basal cells from nasopharyngeal (NP) aspirates of newborn infants in organotypic cultures to address this issue. We show that pre-term NP progenitors have a markedly distinct molecular signature of a prematurity-associated abnormal program of proliferation and mitochondria quality control compared to term cells. Prematurity differentially inhibited mitochondria respiration and, although it did not prevent cell differentiation it was later associated with differences in mitochondrial and innate immunity-related genes. Together these differences suggested increased sensitivity of pre-term progenitors to environmental stressors compared to term under non-homeostatic conditions.