Abstract
The impact of prematurity on human development and neonatal diseases, such as bronchopulmonary dysplasia, has 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, which is key for adaptation to neonatal life. We developed a minimally invasive methodology for isolation of neonatal basal cells from nasopharyngeal (NP) aspirates and performed functional analysis in organotypic cultures to address this issue. We show that preterm NP progenitors have a markedly distinct molecular signature of abnormal proliferation and mitochondria quality control compared to term progenitors. Preterm progenitors had lower oxygen consumption at baseline and were unable to ramp up consumption to the levels of term cells when challenged. Although they formed a mucociliary epithelium, ciliary function tended to decline in premature cells as they differentiated, compared to term cells. Together, these differences suggested increased sensitivity of preterm progenitors to environmental stressors under non-homeostatic conditions.
Highlights
The impact of prematurity on human development and neonatal diseases, such as bronchopulmonary dysplasia, has been widely reported
Are the intrinsic programs of self-renewal and cell fate of basal cells affected by premature birth in infants? If so, how and to which extent this impairs the ability to form specific cell types? If exposed to the same physiologic normal conditions can premature and mature stem cell develop ? These compelling questions are of high significance but difficult to systematically address
Nasopharyngeal aspirates from newborns are a source of epithelial progenitors for studying the stem cell program of the upper respiratory tract
Summary
The impact of prematurity on human development and neonatal diseases, such as bronchopulmonary dysplasia, has been widely reported. Preterm progenitors had lower oxygen consumption at baseline and were unable to ramp up consumption to the levels of term cells when challenged They formed a mucociliary epithelium, ciliary function tended to decline in premature cells as they differentiated, compared to term cells. The transition from prenatal to postnatal life imposes major challenges to the epithelium that must respond to the markedly different hyperoxic environment triggered by the first breath, as well as have an innate immune mechanism able to handle exposure to biological agents not present during intrauterine life Given that these depend on differentiation/maturation events that are completed largely by the end of the third trimester, premature birth can be associated with respiratory diseases of the neonate with increased morbidity and mortality. These opportunities would not occur in healthy term or preterm newborns in neonatal intensive care unit (NICU) settings
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