The proportion of alveolar type 1 cells decreases in murine hypoplastic congenital diaphragmatic hernia lungs
Nguyen, Tram Mai ; Jimenez, Julio ; Rendin, Linda Elowsson LU ; Müller, Catharina LU ; Westergren-Thorsson, Gunilla LU
; Deprest, Jan
and Toelen, Jaan
(2019)
In PLoS ONE
14(4).
- Abstract
Background Pulmonary hypoplasia, characterized by incomplete alveolar development, remains a major cause of mortality and morbidity in congenital diaphragmatic hernia. Recently demonstrated to differentiate from a common bipotent progenitor during development, the two cell types that line the alveoli type 1 and type 2 alveolar cells have shown to alter their relative ratio in congenital diaphragmatic hernia lungs. Objective We used the nitrofen/bisdiamine mouse model to induce congenital diaphragmatic hernia and accurately assess the status of alveolar epithelial cell differentiation in relation to the common bipotent progenitors. Study design Pregnant Swiss mice were... (More)
(Less)
Background Pulmonary hypoplasia, characterized by incomplete alveolar development, remains a major cause of mortality and morbidity in congenital diaphragmatic hernia. Recently demonstrated to differentiate from a common bipotent progenitor during development, the two cell types that line the alveoli type 1 and type 2 alveolar cells have shown to alter their relative ratio in congenital diaphragmatic hernia lungs. Objective We used the nitrofen/bisdiamine mouse model to induce congenital diaphragmatic hernia and accurately assess the status of alveolar epithelial cell differentiation in relation to the common bipotent progenitors. Study design Pregnant Swiss mice were gavage-fed with nitrofen/bisdiamine or vehicle at embryonic day 8.5. The administered dose was optimized by assessing the survival, congenital diaphragmatic hernia and facial abnormality rates of the exposed mouse pups. NanoCT was performed on embryonic day 11.5 and 16.5 to assess the embryonic and early canalicular stages of lung development. At embryonic day 17.5 corresponding to late canalicular stage, congenital diaphragmatic hernia lungs were characterized by measuring the lung weight/ body weight ratio, morphometry, epithelial cell marker gene expression levels and alveolar cell type quantification. Results Nitrofen/bisdiamine associated congenital diaphragmatic hernia lungs showed delayed development, hypoplasia with morphologic immaturity and thickened alveolar walls. Expression levels of distal epithelial progenitor marker Id2 increased, alveolar type 1 cell markers Pdpn and Hopx decreased, while type 2 cell markers pro-SPC and Muc1 remained constant during the canalicular stage. The number of Pdpn
+
type 1 alveolar cells also decreased in congenital diaphragmatic hernia lungs. Conclusion The mouse nitrofen/bisdiamine model is a potential model allowing the study of congenital diaphragmatic hernia lung development from early stages using a wide array of methods. Based on this model, the alveolar epithelium showed a decrease in the number of alveolar type 1 cell in congenital diaphragmatic hernia lungs while type 2 cell population remains unchanged.
- author
- Nguyen, Tram Mai
; Jimenez, Julio
; Rendin, Linda Elowsson
LU
; Müller, Catharina
LU
; Westergren-Thorsson, Gunilla
LU
; Deprest, Jan
and Toelen, Jaan
- organization
- publishing date
- 2019-04-17
- type
- Contribution to journal
- publication status
- published
- subject
- in
- PLoS ONE
- volume
- 14
- issue
- 4
- article number
- e0214793
- publisher
- Public Library of Science (PLoS)
- external identifiers
-
- pmid:30995255
- scopus:85064454961
- ISSN
- 1932-6203
- DOI
- 10.1371/journal.pone.0214793
- language
- English
- LU publication?
- yes
- id
- 427e4990-bf01-483a-8562-4b44f49c2fe8
- date added to LUP
- 2019-05-03 13:28:18
- date last changed
- 2024-09-17 19:19:00
@article{427e4990-bf01-483a-8562-4b44f49c2fe8,
abstract = {{<p><br>
Background Pulmonary hypoplasia, characterized by incomplete alveolar development, remains a major cause of mortality and morbidity in congenital diaphragmatic hernia. Recently demonstrated to differentiate from a common bipotent progenitor during development, the two cell types that line the alveoli type 1 and type 2 alveolar cells have shown to alter their relative ratio in congenital diaphragmatic hernia lungs. Objective We used the nitrofen/bisdiamine mouse model to induce congenital diaphragmatic hernia and accurately assess the status of alveolar epithelial cell differentiation in relation to the common bipotent progenitors. Study design Pregnant Swiss mice were gavage-fed with nitrofen/bisdiamine or vehicle at embryonic day 8.5. The administered dose was optimized by assessing the survival, congenital diaphragmatic hernia and facial abnormality rates of the exposed mouse pups. NanoCT was performed on embryonic day 11.5 and 16.5 to assess the embryonic and early canalicular stages of lung development. At embryonic day 17.5 corresponding to late canalicular stage, congenital diaphragmatic hernia lungs were characterized by measuring the lung weight/ body weight ratio, morphometry, epithelial cell marker gene expression levels and alveolar cell type quantification. Results Nitrofen/bisdiamine associated congenital diaphragmatic hernia lungs showed delayed development, hypoplasia with morphologic immaturity and thickened alveolar walls. Expression levels of distal epithelial progenitor marker Id2 increased, alveolar type 1 cell markers Pdpn and Hopx decreased, while type 2 cell markers pro-SPC and Muc1 remained constant during the canalicular stage. The number of Pdpn <br>
<sup>+</sup><br>
type 1 alveolar cells also decreased in congenital diaphragmatic hernia lungs. Conclusion The mouse nitrofen/bisdiamine model is a potential model allowing the study of congenital diaphragmatic hernia lung development from early stages using a wide array of methods. Based on this model, the alveolar epithelium showed a decrease in the number of alveolar type 1 cell in congenital diaphragmatic hernia lungs while type 2 cell population remains unchanged. <br>
</p>}},
author = {{Nguyen, Tram Mai and Jimenez, Julio and Rendin, Linda Elowsson and Müller, Catharina and Westergren-Thorsson, Gunilla and Deprest, Jan and Toelen, Jaan}},
issn = {{1932-6203}},
language = {{eng}},
month = {{04}},
number = {{4}},
publisher = {{Public Library of Science (PLoS)}},
series = {{PLoS ONE}},
title = {{The proportion of alveolar type 1 cells decreases in murine hypoplastic congenital diaphragmatic hernia lungs}},
url = {{http://dx.doi.org/10.1371/journal.pone.0214793}},
doi = {{10.1371/journal.pone.0214793}},
volume = {{14}},
year = {{2019}},
}