Dynamic changes of lung homeostasis from development-to-aging single-cell atlas
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE260769 | GEO | 2024/03/10
REPOSITORIES: GEO
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2021-01-19 | BIOMD0000000984 | BioModels
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2021-11-30 | PXD021884 | Pride
Project description:Our data demonstrates enrichment of the GO term extracellular region among the decreased lung transcripts of JF1 throughout the process of lung development and maturation in consistent to the altered elastin to collagen ratio. Our microarray data showed increased ~4 fold increased elastin transcripts in JF1 lungs at P70. Specific CL‐saline/air ratio in JF1 mice compared to C3H (JF1-male: 2.68±01.10 versus C3H-male: 2.15±0.42, p<0.05; JF1-female: 3.22±0.88 versus C3H-female: 2.27±0.23, p<0.05) suggests that surface tension contributes more than the elastic recoiling properties of lung in determining the lung compliance as assessed by air filling. This observation is consistent with the smaller alveolar size of JF1 mice. The lower ratio (specific compliance) of CLAir/TLC and CLSaline/TLC in JF1 indicates that elastic recoil due to tissue properties is higher in JF1 compared to C3H. Therefore, the two phenomenon results in a less compliant lung due to higher surface tension in the alveoli and higher elastic recoil due to tissue properties in JF1 compared to C3H. Therefore, the lung architecture, lung function and molecular data of the two strains are in agreement with each other.
2017-07-26 | GSE80078 | GEO
Project description:Background. Animal models of elastase intratracheal instillation have shown that elastase, unopposed by α-1 antitrypsin (AAT), can induce alveolar hemorrhage with ensuing macrophage inflammation and lung damage. Aim. To identify markers of alveolar hemorrhage and damage using bronchoalveolar lavage (BAL) samples and lung tissue explants from AAT deficient (AATD) subjects. Methods. BAL samples (17 patients, 15 controls) were evaluated for free heme and iron concentrations. Alveolar macrophage (AlvMac) activation patterns were assessed by RNA sequencing and validated in vitro using heme-stimulated monocyte-derived macrophages (MDM). Lung explants (7 patients, 4 controls) were evaluated for iron sequestration patterns, by Prussian blue stain and ferritin immunohistochemistry, and for ferritin iron imaging and elemental analysis by electron microscopy (EM). Tissue oxidative damage was assessed by 8-OHdG immunohistochemistry. Results. BAL showed significantly elevated free heme and iron concentrations at lobar level. BAL macrophage RNA sequencing showed innate proinflammatory activation, consistent with free heme activation. AATD tissue alveolar and interstitial macrophages showed elevated iron and ferritin accumulation in large lysosomes packed with iron oxide cores with degraded ferritin protein cages. AATD explants showed massive oxidative DNA damage in lung epithelial cells and macrophages. Conclusions. Identification of BAL and tissue markers of alveolar hemorrhage, together with the molecular and cellular evidence of macrophage innate pro-inflammatory activation and oxidative damage, consistent with free heme stimulation, provides ex vivo evidence for the pathogenetic role of elastase-induced alveolar hemorrhage AATD emphysema as shown in animal studies.
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