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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Main Authors: Jessica E. Shui, Wei Wang, Helu Liu, Anna Stepanova, Grace Liao, Jun Qian, Xingbin Ai, Vadim Ten, Jining Lu, Wellington V. Cardoso
Format: Article
Language:English
Published: Nature Publishing Group 2021-05-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-021-90093-x
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spelling 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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