Division of Neonatology and Newborn Medicine, Department of Pediatrics, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Columbia Center for Human Development, Pulmonary Allergy & Critical Care Medicine, Department of Medicine, Columbia University Irving Medical Center, 650 West 168th Street, BB 8-812, New York, NY, 10032, USA.
Sci Rep. 2021 May 24;11(1):10799. doi: 10.1038/s41598-021-90093-x.
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.
早产对人类发育和新生儿疾病（如支气管肺发育不良）的影响已被广泛报道。然而，对于早产对呼吸道上皮细胞干细胞自我更新和分化程序的影响，人们知之甚少，而这对适应新生儿生活至关重要。我们开发了一种从鼻咽抽吸物中分离新生儿基底细胞的微创方法，并在器官型培养中进行了功能分析，以解决这个问题。我们发现，与足月的祖细胞相比，早产的 NP 祖细胞具有明显不同的增殖和线粒体质量控制的分子特征。与足月祖细胞相比，早产祖细胞的基础耗氧量较低，当受到挑战时，它们无法将耗氧量提高到足月细胞的水平。尽管它们形成了黏液纤毛上皮，但与足月细胞相比，在分化过程中，早产细胞的纤毛功能往往会下降。这些差异表明，在非稳态条件下，早产祖细胞对环境应激源的敏感性增加。
