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

Area of Science:

• Neonatal development
• Respiratory medicine
• Stem cell biology

Background:

• Prematurity impacts neonatal development and diseases like bronchopulmonary dysplasia.
• The effects of prematurity on upper airway stem cell self-renewal and differentiation remain unclear.
• The upper respiratory epithelium is crucial for neonatal adaptation.

Purpose of the Study:

• To investigate the impact of prematurity on neonatal basal cells from the upper respiratory tract.
• To analyze the self-renewal and differentiation programs of preterm versus term respiratory stem cells.
• To assess functional differences in respiratory progenitors under varying conditions.

Main Methods:

• Developed a minimally invasive method to isolate neonatal basal cells from nasopharyngeal aspirates.
• Utilized organotypic cultures for functional analysis of isolated cells.
• Compared molecular signatures, proliferation, mitochondrial function, and differentiation capacity of preterm and term progenitors.

Main Results:

• Preterm nasopharyngeal progenitors exhibit distinct molecular signatures indicating abnormal proliferation and mitochondrial quality control.
• Preterm progenitors show reduced baseline oxygen consumption and impaired response to metabolic challenges compared to term cells.
• While forming mucociliary epithelium, preterm cells displayed declining ciliary function during differentiation.

Conclusions:

• Preterm respiratory stem cells possess altered functional properties, including impaired mitochondrial respiration and reduced ciliary function.
• These progenitor cells exhibit heightened sensitivity to environmental stressors, particularly under non-homeostatic conditions.
• Findings suggest potential long-term implications for respiratory health in individuals born prematurely.