Prematurity alters the progenitor cell program of the upper respiratory tract of neonates
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, wh...
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doaj-553bcca3e5344c2da2c372b094691afd2021-05-30T11:38:13ZengNature Publishing GroupScientific Reports2045-23222021-05-0111111510.1038/s41598-021-90093-xPrematurity alters the progenitor cell program of the upper respiratory tract of neonatesJessica E. Shui0Wei Wang1Helu Liu2Anna Stepanova3Grace Liao4Jun Qian5Xingbin Ai6Vadim Ten7Jining Lu8Wellington V. Cardoso9Division of Neonatology and Newborn Medicine, Department of Pediatrics, Massachusetts General Hospital, Harvard Medical SchoolDivision of Neonatology and Newborn Medicine, Department of Pediatrics, Massachusetts General Hospital, Harvard Medical SchoolColumbia Center for Human Development, Pulmonary Allergy & Critical Care Medicine, Department of Medicine, Columbia University Irving Medical CenterDivision of Neonatology, Department of Pediatrics, Columbia University Irving Medical CenterColumbia Center for Human Development, Pulmonary Allergy & Critical Care Medicine, Department of Medicine, Columbia University Irving Medical CenterColumbia Center for Human Development, Pulmonary Allergy & Critical Care Medicine, Department of Medicine, Columbia University Irving Medical CenterDivision of Neonatology and Newborn Medicine, Department of Pediatrics, Massachusetts General Hospital, Harvard Medical SchoolDivision of Neonatology, Department of Pediatrics, Columbia University Irving Medical CenterDivision of Lung Diseases, NHLBI, NIHColumbia Center for Human Development, Pulmonary Allergy & Critical Care Medicine, Department of Medicine, Columbia University Irving Medical CenterAbstract 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.https://doi.org/10.1038/s41598-021-90093-x |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Jessica E. Shui Wei Wang Helu Liu Anna Stepanova Grace Liao Jun Qian Xingbin Ai Vadim Ten Jining Lu Wellington V. Cardoso |
spellingShingle |
Jessica E. Shui Wei Wang Helu Liu Anna Stepanova Grace Liao Jun Qian Xingbin Ai Vadim Ten Jining Lu Wellington V. Cardoso Prematurity alters the progenitor cell program of the upper respiratory tract of neonates Scientific Reports |
author_facet |
Jessica E. Shui Wei Wang Helu Liu Anna Stepanova Grace Liao Jun Qian Xingbin Ai Vadim Ten Jining Lu Wellington V. Cardoso |
author_sort |
Jessica E. Shui |
title |
Prematurity alters the progenitor cell program of the upper respiratory tract of neonates |
title_short |
Prematurity alters the progenitor cell program of the upper respiratory tract of neonates |
title_full |
Prematurity alters the progenitor cell program of the upper respiratory tract of neonates |
title_fullStr |
Prematurity alters the progenitor cell program of the upper respiratory tract of neonates |
title_full_unstemmed |
Prematurity alters the progenitor cell program of the upper respiratory tract of neonates |
title_sort |
prematurity alters the progenitor cell program of the upper respiratory tract of neonates |
publisher |
Nature Publishing Group |
series |
Scientific Reports |
issn |
2045-2322 |
publishDate |
2021-05-01 |
description |
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. |
url |
https://doi.org/10.1038/s41598-021-90093-x |
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